The Paul Ehrlich Institute (German: Paul-Ehrlich-Institut – Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel, PEI) is a German federal agency, medical regulatory body and research institution for vaccines and biomedicines. It was founded in 1896 and is subordinate to the Federal Ministry of Health. The institute is a WHO Collaborating Centre for quality assurance of blood products and in vitro diagnostic devices. It is located in Langen, Hesse, near Frankfurt, and was located in Frankfurt for most of the 20th century. It is named for its founding director, the immunologist and Nobel Prize laureate Paul Ehrlich..
Abstract Despite the clinical success of CD19-directed CAR T-cell therapies, less than 50% of patients achieve long-term remission. Emerging evidence indicates that loss or reduced expression of CD19—due to mutations, deletions, alternative splicing—is a significant, underrecognized mechanism of treatment failure. Notably, CD19-negative subpopulations can be detected even prior to therapy, and patients with low CD19 expression consistently show poorer outcomes. Although current clinical guidelines do not mandate routine CD19 testing before treatment, this situation reflects both scientific and technical challenges. Importantly, patients with partial/ low CD19 expression may still benefit from therapy, complicating the definition of “target positivity.” From a regulatory perspective, targeted therapies should ideally be used only when target expression is confirmed. This principle is difficult to implement, considering the scarcity of data and the difficulties of current diagnostic tools, risking both undertreatment and overtreatment. EU regulators have addressed the issue by introducing harmonized warnings in product information, but more is needed. We highlight this regulatory-clinical gap and advocate for improved diagnostic standards, better data integration, and dialogue among clinicians, developers, and regulators.
In a process termed trained immunity activated dendritic cells (DCs) and macrophages undergo distinct metabolic changes that contribute to their effector function: While certain activated DC subsets and M1 macrophages undergo a switch towards higher rates of glycolysis and a “disrupted Krebs cycle” to produce important immune effector molecules, alternatively activated (M2) macrophages, plasmacytoid DCs (pDCs), and conventional DCs type 1 (cDC1s) can rely on oxidative phosphorylation for their effector function. DCs and macrophages are also important cells in allergic reactions. While the induction of trained immune responses by microbial stimuli and vaccines is meanwhile well characterized, the contribution of trained immunity to either the establishment, elicitation, or treatment of allergic responses is largely unknown. In this context, recent results suggest distinct trained immunity responses to be established in allergic children. Here it seems that infections early in life predispose to the latter development of allergies, and trained immunity to also contribute to the immune modulation occurring in allergic patients during allergen-specific immunotherapy. Therefore, better understanding of trained immunity in these antigen-presenting cell (APC) subsets may allow to establish new biomarkers and enable a more targeted and efficient treatment of allergic diseases. This article summarizes the specific immune metabolic alterations observed in activated DCs and macrophages explaining their connection to DC and macrophage effector function. It then discusses our current knowledge on the contribution of trained immune responses in the establishment and treatment of allergic diseases.
Regulation (EU) 2024/1938 on quality and safety standards for substances of human origin intended for human application (Substances of Human Origin, SoHO Regulation) represents a paradigm shift in the legal classification of human milk. This review article presents the innovations compared to previous regulations of human milk, describes current European harmonization efforts as well as the state of national implementation,and summarizes the possible impacts of the regulation on the clinical handling of human milk. Overall, new requirements arise for the handling of human milk, particularly with regard to an obligation for registration of entities that carry out a SoHO activity and for authorization as a SoHO establishment.It should be noted that Regulation (EU) 2024/1938 applies not only to the handling of donor human milk but also to the handling of processed mother's own milk.A transition phase until August 2028 enables gradual implementation while taking into account European harmonization efforts and national challenges
The accurate identification of gametes, embryos, and patients is a fundamental requirement for the intended treatment in the context of assisted reproductive technology (ART). Embryo mix-ups are among the most serious errors in ART and are considered highly sensitive, which can impede error management and the identification of error sources. Here, we present five cases of embryo mix-ups that occurred at five different ART facilities. These reports highlight misidentification of patients and specimens as underlying factors in all five mix-up cases and emphasize the importance of facility-wide root cause analysis to improve process safety for patients and staff. Although human error was an important factor, the underlying conditions that make these critical errors possible must be identified to allow for effective risk mitigation. In all cases, a sequence of errors led to embryo mix-ups that could have been prevented by adherence to clear institutional guidelines and workflows regarding patient identification and verification of patient and sample identities prior to embryo transfer. It is important that operating guidelines are integrated into daily work routines and ART facilities have control systems in place to monitor critical steps and allow for the detection of error sources or faulty processes to prevent subsequent damage.
Vaccine pharmacovigilance is critically important to ensure transparent information related to vaccine safety. We conducted a prospective, non-interventional, population-based cohort study, SafeVac2.0, in order to supplement passive surveillance of COVID-19 vaccines by collecting self-reported adverse events (AEs). Participation via smartphone app was allowed within 48 h after the administration of the first or second dose of a COVID-19 vaccine. Adverse events were collected up to 3 weeks after the first vaccination, 8 weeks after the second vaccination, and 7 days after the booster dose. Participants were also asked about their health condition 6 and 12 months after the first dose registered. The study was conducted from December 26, 2020 to September 30, 2022. A total of 739,216 persons met the primary inclusion criteria, of which 732,864 documented at least one vaccination. Data on 1,436,039 vaccinations were collected. At least one AE was reported for 68% of the vaccinations and in total 4,007,149 AEs were reported. 88% of AEs consisted of solicited local and systemic reactogenicity. Age, sex, vaccine product and dose were potential predictors for solicited adverse events. The need for medical care was reported in 0.36% of vaccinations. Overall, the study results provide reassurance of the safety profile of COVID-19 vaccines. The use of a native app to monitor self-reported adverse events represents an innovative pharmacovigilance approach.
