Euro Roundup: EMA finalizes companion diagnostic advice


| July 07, 2022 | By Nick Paul Taylor


The European Medicines Agency (EMA) has finalized guidance on companion diagnostics, addressing procedural aspects to facilitate consultation between the EMA and the Notified Body as part of the conformity assessment process.

As part of conformity assessments, notified bodies must ask the EMA or a competent authority for a scientific opinion on the suitability of the companion diagnostic for use with the medicinal product concerned. Notified Bodies must consult EMA when the medicinal product falls within the mandatory scope of the centralized procedure. The guide contains advice on the EMA procedure for initial and follow-up consultations.

The EMA published a draft version of the text for consultation at the end of last year. Organizations such as EFPIA (the European Federation of Pharmaceutical Industries and Associations) and MedTech Europe have submitted comments on the draft. MedTech Europe provided brief comments, noting that it is “conscious not to slow down the publication” of a guidance document which it considers essential to ensure the smooth running of the consultation process.

The EFPIA provided more in-depth feedback, although some of its main points fell outside the scope of the EMA’s role. The trade group said it is “strongly” convinced that the marketing authorization holder “should be involved in communication at every stage of the process, including the pre-submission meeting”, adding that It is essential that all parties are aware of the consultation and pre-submission. -submission schedule. The EMA has refocused attention on the developers of the drug and the companion diagnostic.

“It is not within EMA’s remit to actively inform or involve the device manufacturer or MAHs and drug applicants in this process. It is the responsibility of the MAH/applicant and the device manufacturer to coordinate the sharing of information on their respective applications and to keep each other informed of the stages of their applications,” according to the EMA’s response to the comment of the EFPIA.

Still, the EMA has made changes that appear to reflect EFPIA’s comments, noting in a new sub-section on early interactions that all parties involved are recommended to “align the timeline” for approval. drug and device certification in co-development scenarios.

The changes are part of the EMA’s overhaul of the guide’s main section on practice recommendations. The final guidelines include an introductory paragraph that explains that the consultation process has four distinct phases: pre-submission, submission, evaluation and post-consultation. EMA has made significant changes to the text of each phase, including adding a paragraph on co-developed companion diagnostics to the application and scope section of the submission phase.

By finalizing and adopting the guidance six months after the start of the consultation and putting the text into effect as soon as it is published, the EMA has truncated the usual timetable, potentially reflecting calls from groups such as MedTech Europe to adopt the document without time limit.

Final direction, comments submitted

Swissmedic Creates Position Paper on Real-World Evidence to Offer “Initial Points” to Industry

The Swiss Agency for Therapeutic Products (Swissmedic) has published a position paper to “offer some initial guidance to applicants” who wish to use real-world evidence (RWE) in their filings.

There is no legal basis for including RWE in drug authorization in Switzerland, where therapeutic products legislation requires data from trials in accordance with good clinical practice to support approvals, according to Swissmedic . Despite this, with international guidelines giving “some prominence to RWE in some cases”, the agency has publicly stated its position.

Applicants submitting RWE should summarize their rationale in their cover letter and present their argument in detail in the dossier. Swissmedic expects applicants to critically discuss the RWE in the context of all available evidence.

In new marketing authorization and variation applications, Swissmedic accepts RWE “in addition to clinical trial data”, for example, as a control group to contextualize and substantiate study results. The agency will not accept new marketing authorization applications based on RWE. Elsewhere, Swissmedic discusses the use of RWE for post-market surveillance and its data quality requirements.

Swissmedic paper

Commission publishes implementing regulation on specifications for Class D diagnostics

The European Commission has published an implementing regulation establishing common specifications for certain in vitro diagnostics (IVDs), including products used to detect or quantify markers of HIV and hepatitis infection.

Previously, there was a lack of harmonized standards with regard to the requirements of Annex I of the In Vitro Diagnostics Regulation (IVDR), which sets out general safety and performance requirements. To fill this gap, the Commission has created common specifications for class D IVDs for a range of infectious diseases.

The document has a section on general common specifications, which covers topics such as how to determine the performance characteristics and failure rate of the entire system, and then focuses on IVDs against a range of infectious diseases. In the HIV subsection, the Commission outlines the number and type of positive specimens that IVD test developers should use to determine diagnostic sensitivity.

Until July 25, 2024, European authorities will presume that IVDs complying with the common technical specifications of the old directive or the new regulation comply with the relevant parts of Annex I of the IVDR. The implementing regulations will enter into force on July 25, 2024.


EMA answers questions about the removal and replacement of titanium dioxide excipient

EMA has answered frequently asked questions about the removal and replacement of the excipient titanium dioxide, explaining the implications of the regulatory changes adopted earlier this year.

In January, European officials agreed to change food additives legislation following a report by the food safety regulator which concluded that it was impossible to rule out the genotoxicity of titanium dioxide as a food additive. The new regulation provides that the excipient will remain on the list of products authorized for medicinal products in order to avoid shortages.

The Q&A explains that companies that have filed or are about to file for approval of products containing titanium dioxide can continue to include the excipient in their formulations. However, the EMA wants marketing authorization holders to “make every effort to accelerate research and development of alternatives and to replace” titanium dioxide in their authorized products.

The EMA said “it is essential that manufacturers collaborate with each other regarding the research and development of alternatives” and define the data requirements for removal and replacement.


EDQM invites comments on revisions to heparin monographs and other draft proposals

The European Directorate for the Quality of Medicines and Healthcare (EDQM) has published draft versions of its monographs on heparin sodium and heparin calcium for consultation.

The monographs on heparin date from the 1980s, making them one of the oldest in the European Pharmacopoeia, and underwent major revisions after the adulteration scandal of 2008. Today, the EDQM invites comments on further changes to clarify declarations on the control of the absence of porcine source materials, a topic that was subject to public consultation in 2021. The projects also propose to lower the limit residual protein to 0.1% or less.

The EDQM has distinguished the heparin monographs from the batch of draft documents put out for consultation in Pharmeuropa 34.3. The comment window on all draft monographs is open until September 30.

EDQM Reviews, More

© 2022 Society of Regulatory Affairs Professionals.


Comments are closed.