Euro Roundup: EMA finalizes guideline on monitoring drug safety in pregnant and breastfeeding women

The European Medicines Agency (EMA) has finalized its guideline on good pharmacovigilance practices about the risks to children exposed to medicines by pregnant and breastfeeding women in utero or via breastmilk.

EMA released a draft chapter on pharmacovigilance for medicines used by pregnant and breastfeeding women for public consultation in 2019. The agency published 371 pages of feedback on the draft in 2020. Six years after ending the consultation, EMA has finalized the document, which came into effect on 9 February. The document incorporates an earlier guideline on post-authorization pregnancy data.

The agency has made extensive changes to the draft to reflect feedback from organizations including the pharma trade group EFPIA. EMA changed the name of a subsection from “pregnancy registries” to “data sources” and expanded the scope of evidence that companies can use.

EFPIA told EMA that pregnancy registries have “proven to be very challenging to conduct because of the slow enrolment.” The trade group called for EMA to provide guidelines or basic principles about when companies should consider using pregnancy registries. EMA’s final guideline recommends the use of existing data sources, including registries, to enhance long-term follow-up.

The agency also changed how signals are handled in EudraVigilance. EFPIA questioned how pregnancy signals will be handled in the EudraVigilance Data Analysis System given the competing endpoints, very low incidence of individual birth defects, and multiple prevalence categories.

In its final guideline, EMA said the standardized MedDRA query for pregnancy and neonatal topics may be too broad and suboptimal in some cases. The agency recommended companies consider using its rule-based algorithm in EudraVigilance “to more efficiently retrieve reported cases of suspected adverse reactions during pregnancy, thereby reducing the burden of manually excluding irrelevant cases.”

Other changes that reflect EFPIA feedback include the addition of a definition of miscarriage and tweaks to advice on lactation studies. EFPIA said the medicinal product itself will not be excreted in breast milk, explaining that the active pharmaceutical ingredient and, if applicable, its metabolites are the substances of interest. The final text addresses measuring active substance levels in breast milk.

EMA Guideline, More

Notified bodies raise concerns about plans to add cybersecurity rules to MDR and IVDR

A notified body trade association has raised concerns about plans to include more granular cybersecurity requirements in the European Union medtech regulations.

The association, Team-NB, said the Medical Device Regulation (MDR) and In Vitro Diagnostic Regulation (IVDR) are “designed to adapt to innovation and changes of their environment by means of (harmonized) standards, common specifications, and regulatory guidance.” Relying on standards and guidance allows for deviations when adequately justified, the association said. Passing laws could end that flexibility.

Team-NB said it welcomes revision and further development of the European cybersecurity framework for medical devices based on guidance and harmonized standards. However, the group cautioned against “granular technical requirements in our regulations that will be outdated faster than any legislator may update them.”

The association said notified bodies fear inflexible legal rules will fail to improve, and potentially hinder, cybersecurity while decreasing European patients’ access to innovative medical devices. Notified bodies are similarly concerned that extending the Cyber Resilience Act’s framework to devices would impose disproportionate burdens while delivering incremental cybersecurity improvements, at best.

“Such an additional overlap of governance in the area of medical device software is very likely to cause SMEs to further reduce their involvement in the European market and thus reduce competition between manufacturers and availability of medical devices for patients and practitioners,” Team-NB said.

The association said an exchange and crosstalk between regulatory frameworks as proposed by the European Commission in its draft revision of MDR and IVDR is “a more practicable and yet satisfactory solution.” Team-NB also defended the suitability of MDR and IVDR’s “state-of-the-art” principle as a way to support cybersecurity.

Because cybersecurity is a never-ending competition between defenders and attackers, state-of-the-art as a concept might be even more important for the sector than in other less dynamic fields, Team-NB said. The ongoing evolution of threats informed Team-NB’s belief that cybersecurity can never be a compliance exercise of simply fulfilling requirements. Instead, cybersecurity must be seen as a process.

Team-NB Letter

MHRA addresses impact of new EU regulation on pharmacovigilance practices in the UK

The Medicines and Healthcare products Regulatory Agency (MHRA) has advised marketing authorization holders about how changes in the EU will affect pharmacovigilance in the UK.

As a result of a Brexit agreement, the UK has an independent regulatory framework that classifies drugs into two technical categories. One category covers medicines that previously fell within the mandatory or optional scope of the EU’s centralized procedure. Medicines in the other category, which covers all other products, follow additional EU pharmacovigilance requirements set out in CIR 520/2012.

European Commission changes to CIR 520/2012 took effect this week, creating misalignments between the EU and UK rules. MHRA said the changes have implications for companies that have drugs covered by CIR 520/2012 or hold licenses in both the UK and the EU.

To mitigate the impact of the regulatory divergence, MHRA has asked companies to follow the amended CIR 520/2012 requirements for both categories of products. Companies with products that previously fell within the mandatory or optional scope of the EU’s centralized procedure can follow the UK legislation if they lack equivalent licenses in the EU.

MHRA Notice

Trade groups find regulatory barriers to electronic product information pilot projects

EFPIA has found legal and regulatory barriers to the implementation of electronic product information (ePI) pilot projects in several countries.

The trade group highlighted the barriers after writing an ePI report with its counterparts AESGP and Medicines for Europe. The report provides an overview of ePI pilot projects in 31 countries. While the authors found cause for cautious optimism ahead of the move away from paper, they also uncovered barriers to ePI adoption in some countries. Bulgaria is one country where regulations are an issue.

“There are concerns about the limited technical infrastructure and digital readiness within regulatory bodies and the healthcare system, which hinder the deployment of ePI,” the trade groups wrote. “Regulatory uncertainty and a lack of clear guidance on ePI implementation, governance, and alignment with EU frameworks further complicate the situation.”

The trade groups said legal obstacles and constraints are among the main reasons why countries have not conducted ePI pilots. Other issues include the lack of capacity or resources at local authorities or the absence of a database capable of keeping up-to-date ePI.

EFPIA Notice

Other News:

The Swiss Agency for Therapeutic Products (Swissmedic) has activated the legacy device feature on its swissdamed database. Activating the feature allows companies to register devices covered by the outgoing medtech directives on the database. Swissmedic has updated the swissdamed homepage and technical documentation to reflect the new feature. Swissmedic Notice

MHRA has concluded a pilot of its real-world evidence (RWE) scientific dialogue program. The agency is now reviewing the findings of the pilot and exploring options for continuing the program. During the pilot, MHRA selected four applicants for closed-door, confidential meetings about a range of RWE topics, disease areas, and stages of the drug product lifecycle. MHRA Notice

Euro Roundup: EMA finalizes guideline on monitoring drug safety in pregnant and breastfeeding women

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