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Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
The European Medicines Agency (EMA) has revised its good pharmacovigilance practice (GVP) guideline after Danish regulators flagged up a “big problem” with a draft version. EMA's change mitigates the risk of marketing authorization holders (MAHs) and national agencies independently merging duplicate safety reports.
In the draft version of module VI of the GVP guidelines, EMA included a chart showing a process for managing individual case safety reports (ICSRs). The chart showed ICSRs being delivered into EMA's EudraVigilance system before being passed on to MAHs and national competent authorities (NCAs). If the MAH or NCA identified a duplicate when adding the ICSR to their databases, EMA's process map called for them to merge the records and tell the transnational agency of their action.
EMA released the process map for consultation along with the rest of the draft guideline one year ago. Now, EMA has published the feedback it received, including comments from the Danish Medicines Agency (DKMA) that strongly question the merits of the approach to merging duplicates.
“The DKMA sees a big problem with the proposed procedure. If both MAHs and NCA are responsible for merging the duplicates, there is the possibility that the different senders will identify the duplicates on the same day and merge them simultaneously,” the Danish regulator wrote.
EMA has acted on the criticism, although its response differs from that proposed by DKMA. The Danish agency suggested giving it and other NCAs sole responsibility for duplicate merging. Under this model, MAHs that discovered duplicates would tell the NCA. The NCA would then decide whether to merge the duplicates.
The model adopted by EMA in its final guideline strips both MAHs and NCAs of the responsibility for merging duplicates. Instead, MAHs and NCAs are to tell EMA when they discover duplicates. EMA will merge the duplicates to create a master case, before telling the MAH and NCA about what it has done. The MAH and NCA will then incorporate the EMA changes into their own local pharmacovigilance databases.
EMA's adoption of a new process for handling duplicates is one of many changes made by the agency following the public consultation. The changes follow the receipt of feedback that pointed out perceived faults with multiple significant aspects of the guideline.
The European Federation of Pharmaceutical Industries and Associations (EFPIA) sent in one of the longer responses to the draft. EFPIA criticized the draft for making the requirements it places upon companies “unnecessarily specific.” The trade group sees this as undesirable given the evolving nature of pharmacovigilance science.
EMA has changed aspects of the guideline in response to EFPIA's feedback. The adopted version features advice on managing ICSRs related to off-label use, which was lacking in the draft. EMA flagged up the failure to incorporate the points made in a 2016 reflection paper on the topic into the draft as a missed opportunity.
In other areas, EMA has gone against the feedback of EFPIA and others. Notably, EFPIA asked EMA to release a revised version incorporating its feedback for consultation. Instead, EMA has adopted a final version without putting it through a second formal public consultation. The revised version is due to come into effect on 22 November.
Final Guideline, Track Changes, Comments
EMA has released draft guidelines detailing how GVPs apply to pediatric populations. The guideline broadens the scope of pharmacovigilance and definition of adverse reaction to bring it in line with legislative changes since the current pediatric regulation came into force in 2007.
The biggest change to pharmacovigilance since the publication of the pediatric regulation came in 2012 when the European Union adopted new legislation on the topic. That extended the definition of adverse reaction to cover harm caused by the deliberate or accidental misuse of drugs. The 2012 text also extended the scope of pharmacovigilance to cover the assessment of the risks of off-label use.
EMA sees both changes as particularly pertinent to pediatric patients and has revised its guideline accordingly. The draft encourages MAHs and NCAs to address the risk a medicine will interfere with school or sports performance or interact with pharmacologically-active substances such as alcohol and nicotine in their communications, if such information is available. EMA also wants the communications to cover the risks of giving medicines to friends.
These issues are completely absent from the 2007 regulation. In contrast, off-label use is discussed extensively in the existing guideline, reflecting the fact many medicines were not adequately tested in or designed for children and adolescents then. The situation has improved somewhat since 2007, resulting in the draft containing fewer references to off-label use than the current text.
The trimmed-down sections on off-label use emphasize the need for reporting systems to gather evidence that supports hypotheses about “whether off-label use can be an independent risk factor in developing adverse reactions.”
EMA created the draft in collaboration with the Heads of Medicines Agencies (HMA). The draft is open for comment until 13 October. EMA and HMA plan to bring a final version into force in the first quarter of next year.
Draft Guidelines, Module VI, Addendum I, Comments
The Swiss Agency for Therapeutic Products (Swissmedic) is set to move its Certificates of Pharmaceutical Product (CPP) ordering service to the eGovernment Portal. Swissmedic will switch to the new system at the start of next year.
Today, organizations that want a CPP send an order form via email. Swissmedic will close off this option in five months and instead make companies go through the eGov Portal. Companies will receive CPPs by post, as they do under the current, email-based system, and will also receive a note confirming their successful order in their eGov CPP service inbox.
Swissmedic is encouraging companies to apply to access the eGov service before its use becomes mandatory for requesting CPPs.
The transition of CPP requests to eGov is part of a planned phased rollout of the portal. Swissmedic is also preparing to move applications related to clinical trials, non-conforming medical devices and exports to the portal.
EMA has released a guide to help rapporteurs and coordinators set up multinational assessment teams (MNATs). The drafting of the guide follows the expansion of the MNAT concept to include more countries and cover more types of regulatory assessments.
MNATs are assessment teams made up of representatives of NCAs. EMA pays the NCAs that take part in the MNAT for their services. The EU-wide regulator created ground rules for the concept at the turn of the year to support its expansion to the post-authorization phase. The latest document complements that text by providing advice for rapporteurs and coordinators.
EMA has used the guide to walk rapporteurs and coordinators through the steps they need to take when preparing MNATs for either scientific advice, initial evaluation and maximum residue limit applications or post-authorization filings. The details of what steps need to be taken differ depending on whether the submission is pre or post-authorization.
The document also covers contractual arrangements and how to distribute remuneration.
Tags: pharmacovigilance, DKMA, Swissmedic