Euro Roundup: EMA finalizes companion diagnostic guidance

RoundupsRoundups | 07 July 2022 |  By 

The European Medicines Agency (EMA) has finalized guidance on companion diagnostics, addressing procedural aspects to facilitate consultation between EMA and the notified body in the conformity assessment process.
As part of conformity assessments, notified bodies need to seek a scientific opinion on the suitability of the companion diagnostic for use with the concerned medicinal product from either EMA or a competent authority. Notified bodies should consult with EMA when the medicinal product falls within the mandatory scope of the centralized procedure. The guidance features advice on EMA’s procedure for initial and follow-up consultations.
EMA released a draft version of the text for consultation late last year. Organizations including EFPIA (the European Federation of Pharmaceutical Industries and Association) and MedTech Europe submitted comments on the draft. MedTech Europe provided brief feedback, noting that it is “keen not to slow down publication” of a guidance document it views as critical to ensuring the consultation process runs smoothly.
EFPIA provided more extensive feedback, although some of its main points were outside of the scope of EMA’s role. The trade group said it “strongly” feels that the marketing authorization holder “should be involved in the communication in every stage of the process, including the pre-submission meeting,” adding that it is critical all parties are aware of the consultation and pre-submission timeline. EMA turned the focus back onto the developers of the drug and companion diagnostic.
“It is not in the remit of the EMA to actively inform or involve the device manufacturer or the MAHs and applicants of medicinal products in this process. It is the responsibility of the MAH/applicant and device manufacturer to coordinate sharing of information about their respective applications and keep each other informed on steps of their applications,” according to EMA’s response to EFPIA’s comment.
Yet, EMA did make changes that appear to reflect the feedback from EFPIA, noting in a new subsection on early interactions that “all involved parties are recommended to align the timing” of the medicinal product approval and device certification in co-development scenarios.
The changes are part of EMA’s reworking of the guidance’s core section on practical recommendations. The final guidance has an introductory paragraph that explains the consultation process has four distinct phases: pre-submission, submission, assessment and post-consultation. EMA made extensive changes to the text about each phase, including by adding a paragraph about co-developed companion diagnostics to the section on the application and scope of the submission phase.
By finalizing and adopting the guidance six months after starting the consultation, and bringing the text into effect upon publication, EMA has truncated the typical timeline, potentially reflecting the calls from groups such as MedTech Europe to adopt the document without delay.
Final Guidance, Submitted Comments
Swissmedic creates real-world evidence position paper to offer ‘initial pointers’ to industry
The Swiss Agency for Therapeutic Products (Swissmedic) has released a position paper to “offer some initial pointers to applicants” that want to use real-world evidence (RWE) in their filings.
There is no legal basis for the inclusion of RWE in the authorization of medicinal products in Switzerland, where the therapeutic products legislation requires data from trials that comply with good clinical practices to support approvals, according to Swissmedic. Even so, with international guidelines attaching “some importance to RWE in certain cases,” the agency has outlined its position publicly.
Applicants that submit RWE need to summarize their rationale for doing so in their cover letter and make their case in detail in the dossier. Swissmedic expects applicants to critically discuss the RWE in the context of all the available evidence.
In new marketing authorization and variation applications, Swissmedic accepts RWE “as a complement to clinical trial data,” for example, as a control group to contextualize and support the study results. The agency will not accept new marketing authorization applications based on RWE. Elsewhere, Swissmedic discusses the use of RWE for postmarket surveillance and its data quality requirements.
Swissmedic Paper
Commission publishes implementing regulation on specifications for class D diagnostics
The European Commission has released an implementing regulation to lay down 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 respect to the requirements of annex I of the In Vitro Diagnostic Regulation (IVDR), which sets out general safety and performance requirements. To address the gap, the Commission has created common specifications for class D IVDs aimed at a range of infectious diseases.
The document features a section on general common specifications, which addresses topics such as how to determine performance characteristics and the whole system failure rate, and then focuses on IVDs against a series of infectious diseases. In the HIV subsection, the Commission states the number and type of positive specimens that IVD test developers should use to determine diagnostic sensitivity.
Until 25 July 2024, European authorities will presume IVDs that conform to the common technical specifications of the old directive, or the new regulation are in conformity with the relevant parts of annex I of the IVDR. The implementing regulation will come into force on 25 July 2024.
Implementing Regulation
EMA answers questions on the removal and replacement of the excipient titanium dioxide
EMA has answered frequent questions about the removal and replacement of the excipient titanium dioxide, explaining the implications of the regulatory amendments passed early this year.
In January, European officials agreed to amend food additives legislation in the wake of a report by the food safety regulator that found it is impossible to rule out the genotoxicity of titanium dioxide as a food additive. The new regulation foresees the excipient will remain on the list of authorized products for medicinal products to avoid shortages.
The Q&A explains companies that have filed, or are close to filing, for approval of products that contain titanium dioxide can continue to include the excipient in their formulations. However, EMA wants marketing authorization holders “to make all possible efforts to accelerate the research and development of alternatives and to replace” titanium dioxide in their authorized products.
EMA said, “it is essential that manufacturers collaborate with each other regarding research and development of alternatives” and set out the data requirements for removal and replacement.
EDQM seeks feedback on revisions to heparin monographs, other draft proposals
The European Directorate for the Quality of Medicines & Healthcare (EDQM) has released draft versions of its heparin sodium and heparin calcium monographs for consultation.
Monographs on heparin date from the 1980s, making them among the oldest in the European Pharmacopoeia, and underwent significant revisions after the adulteration scandal of 2008. Now, EDQM is seeking feedback on further changes intended to clarify statements on the control for absence of non-porcine source materials, a topic that was the focus of a public consultation in 2021. The drafts also propose lowering the limit for residual protein to 0.1% or lower.
EDQM singled out the heparin monographs from the batch of draft documents released for consultation in Pharmeuropa 34.3. The comment window on all the draft monographs is open until 30 September.
EDQM Notice, More


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