Euro Roundup: MDCG shares guidance on clinical evidence for orphan in vitro diagnostics
The Medical Device Coordination Group (MDCG) has published guidance on how clinical evidence requirements apply to orphan in vitro diagnostics (IVDs).
Orphan IVDs are used in rare diseases or circumstances, for example, to test for uncommon intoxications. The rarity of the diseases and circumstances creates challenges for organizations needing to comply with the IVD Regulation (IVDR), which requires test developers to have a sufficient amount and quality of data to inform a qualified assessment of safety, performance, and clinical benefit.
As MDCG noted, generating clinical performance data for orphan IVDs within a reasonable time frame may be challenging because of limited specimen availability. Given the challenges, MDCG recommended a “balanced and proportionate” application of the IVDR requirements to orphan tests.
The coordination group set out what that means in practice in a two-part guidance document. The first part addresses clinical evidence considerations, such as the acceptability of limitations in premarket clinical performance data for orphan IVDs. The second part covers procedural considerations, including guidance for notified bodies on assessing orphan IVDs.
MDCG advises manufacturers to specify and justify the level of clinical evidence needed to show conformity with relevant general safety and performance requirements. Manufacturers should consider the disease, the unmet medical need, and the expected clinical benefit, balanced against the anticipated risks, when determining the level of clinical evidence required.
Notified bodies should check the orphan status of an IVD as early as possible, for example during the application phase before initial conformity assessment activities. MDCG recommends that notified bodies base their checks on the information provided by the manufacturer and, if applicable, expert panel advice.
Many orphan IVDs are manufactured in-house by health institutions, reflecting the limited commercial viability of the tests. While in-house diagnostics are exempt from many IVDR requirements, the general principles conveyed in the MDCG guidance are relevant to health institutions that manufacture their own tests.
UK updates clinical trial diversity plan guidance in response to pilot findings
A pilot assessment of the UK’s clinical trial inclusion and diversity plans has informed updated guidance on the topic.
The UK Health Research Authority (HRA) recommends sponsors create a plan early in the study design process to ensure clinical trials include people who could be impacted by the findings. Working with the UK Medicines and Healthcare products Regulatory Agency (MHRA), HRA tested the impact of the policy with commercial and non-commercial sponsors of seven studies.
Commercial sponsors found that developing a plan helped them to consider inclusion and diversity in a more structured way and, in some cases, facilitated conversations with sites about patient recruitment. However, the pilot also revealed areas of the draft guidance that would benefit from further clarity or detail.
HRA updated its guidance in response to the findings. In the revised guidance, HRA advises sponsors to develop plans that consider who is affected by the targeted disease, the recruitment goals, and the strategy for recruiting and retaining the proposed population. The plan should also address whether the clinical trial findings will be generalizable to all people affected by the disease.
Based on the feedback, HRA has revised the layout of the guidance to make information easier to find. The changes reflect sponsor feedback that the draft guidance was too “wordy.” Sponsors also suggested that advice on early-phase and rare disease studies could be made more prominent within the guidance.
Starting early next year, HRA will ask more researchers and sponsors to voluntarily submit a plan alongside their clinical trial applications. The submissions will enable HRA to collect further feedback over 12 months to generate evidence on the benefits of developing a plan.
MHRA Statement, Guidance, Pilot Findings
Swissmedic implements 1-year transition to new rules on additional labels
The Swiss Agency for Therapeutic Products (Swissmedic) has established a one-year transitional period for new rules on applying additional labels to the primary packaging of parallel imported products.
Last month, Swissmedic updated its guidance on parallel imports to explicitly clarify that it will not accept the affixing of additional labels to existing foreign primary packaging. The policy applies to labels providing translations of information into the official Swiss languages, irrespective of the primary packaging’s format or material and the positioning of the affixed label.
This week, Swissmedic clarified how the rules apply to companies with approval to affix labels to the primary packaging of parallel imports. Such companies must apply to remove the additional labels within one year. Batches that have already been released are unaffected by the new rule and can continue to be placed on the market and sold. Companies can release new batches with the approved design until the variation procedure is completed.
Swissmedic recommends that marketing authorization holders affected by the transition period plan the changes they need to make and submit their variation applications “in good time.”
MDCG delays Eudamed upload deadline after go-live date slips to December
MDCG has deferred the deadline for uploading safety and performance summaries to Eudamed until 27 March.
The coordination group disclosed the one-month delay in its guidance on the management of summary of safety and clinical performance (SSCP) and summary of safety and performance (SSP) documents. Currently, notified bodies upload the documents when registering certificates. However, responsibility for uploading the documents is switching from notified bodies to manufacturers.
MDCG published a position paper on the management of SS(C)Ps in Eudamed in June. The recent revision to the document retains all of the group’s previous advice but features new transition timelines.
Manufacturers will be able to upload the documents starting in December, compared to from October onward under the previous guidance. MDCG delayed the deadline for uploading the documents from 27 February to 27 March. The coordination group continues to advise manufacturers and notified bodies to align on timelines to fulfill their registration obligations.
PRAC starts immunoglobulin review after rise in reports of allergic reactions
The European Medicines Agency’s (EMA) pharmacovigilance committee is reviewing reports of allergic reactions in recipients of specific batches of human normal immunoglobulin medicines.
Physicians administer the medicines to prevent infections in people with insufficient antibodies, such as individuals with certain immune disorders or blood cancers. Allergic reactions are a known side effect of the products, but reports indicate that the adverse events may be occurring more frequently than expected with specific batches of the medicines.
Initial investigations have failed to determine the cause of recent clusters of allergic reactions, some of which have been potentially life-threatening. EMA’s Pharmacovigilance Risk Assessment Committee will request data from companies marketing the medicines to investigate the possible causes and determine whether actions are needed to reduce the risk.
The committee disclosed the investigation alongside the news that it has started a review of Deanxit, a fixed-dose combination medicine for treating depression and anxiety. Officials are reviewing the safety of the product in response to reports of serious neurological and psychiatric side effects, including movement disorders and memory and thinking problems.
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Swissmedic has updated the human medicinal product categories in its authorization and variation forms. The changes, which took effect on 1 November, reflect the current state of scientific and technical knowledge. Swissmedic Notice