The new IVD Regulation 2017/746: a case study at a large university hospital laboratory in Belgium demonstrates the need for clarification on the degrees of freedom laboratories have to use lab-developed tests to improve patient care.

Objectives: The new European In Vitro Diagnostic (IVD) Regulation 2017/746 (IVDR) restricts the use of lab-developed tests (LDT) after 26th May 2022. There are no data on the impact of the IVDR on laboratories in the European Union. Methods: Laboratory tests performed in UZ Leuven were divided in four groups: core laboratory, immunology, special chemistry, and molecular microbiology testing. Each test was classified as Conformité Européenne (CE)-IVD, modified/off-label CE-IVD, commercial Research Use Only (RUO) or LDT. Each matrix was considered a separate test. Results: We found that 97.6% of the more than 11.5 million results/year were generated with a CE-IVD method. Of the 922 different laboratory tests, however, only 41.8% were CE-IVD, 10.8% modified/off-label CE-IVD, 0.3% RUO, and 47.1% LDT. Off-label CE-IVD was mainly used to test alternative matrices not covered by the claim of the manufacturer (e.g., pleural or peritoneal fluid). LDTs were mainly used for special chemistry, flow cytometry, and molecular testing. Excluding flow cytometry, the main reasons for the use of 377 LDTs were lack of a CE-IVD method (71.9%), analytical requirements (14.3%), and the fact the LDT was in use before CE-IVD available (11.9%). Conclusions: While the large majority of results (97.6%) were generated with a CE-IVD method, only 41.8% of laboratory tests were CE-IVD. There is currently no alternative on the market for 71.5% of the 537 LDTs performed in our laboratory which do not fall within the scope of the current IVD directive (IVDD). Compliance with the IVDR will require a major investment of time and effort.

Laboratory-developed test regulation and the immunocompromised patient: uncertainty ahead.

PURPOSE OF THE REVIEW: Laboratory-developed tests (LDTs) are essential for the clinical care of immunocompromised individuals. These patients often require specialized testing not available from commercial manufacturers and are therefore dependent on the laboratory to create, validate, and perform these assays. Recent paradigm-shifting legislation could alter the way that LDTs are operationalized and regulated. RECENT FINDINGS: On March 5th, 2020 the Verifying Accurate and Leading-Edge In-Vitro Clinical Tests Development Act (VALID) was introduced in the US Congress. This statute would overhaul existing regulatory framework by unifying the oversight of LDTs and commercial in-vitro diagnostic tests (IVDs) through the FDA. If enacted, LDTs would be subject to regulatory requirements like those found in commercial submissions for market review. Stakeholders continue to discuss the details and scope of the proposed legislation in the setting of the Severe Acute Respiratory Syndrome Coronavirus 2 pandemic, where LDTs are integral to the national COVID-19 response. SUMMARY: Congressional lawmakers have introduced legislation to alter the regulatory framework governing LDTs. Moving forward, a balance must be struck to ensure the availability of safe and accurate testing without delays or overregulation that could be harmful to patients. The downstream implications of how VALID and other legislation will impact laboratories, clinicians, and patients warrant close examination.

[Current status and regulation of bioanalytical laboratories engaged in quantifying immunosuppressants for transplant patients in Argentina]. / Estado de situación y regulación de laboratorios bioanalíticos que cuantifican inmunosupresores para trasplantes en Argentina.

Objective Determine the status of analytical laboratories that quantify immunosuppressants in transplant patients who are under therapeutic drug monitoring (TDM) for these drugs in Argentina in order to identify potential perfectible areas for action. Methods A survey of the clinical and analytical TDM centers in Argentina was conducted between September 2013 and November 2014 under the direction of the Garrahan Hospital Clinical Pharmacokinetics Unit and the National Unified Central Institute for Ablation and Implant Coordination. Results A nationally representative sample of 27 clinical and analytical centers was identified, of which 45% were public hospitals. Most of these centers (95%) monitor ciclosporin and tacrolimus, and to a lesser extent, sirolimus and everolimus; a small number of them also monitor mycophenolic acid. The median number of samples of these five drugs analyzed per month was 251 (range: 10-2024). Nearly 60% of the samples were analyzed in private institutions. Only four of the respondents (17%) reported values within the therapeutic margin. Of all the centers, 92% use immunoassay as the analytical methodology. Of the bioanalytical installations that have their own facilities, 68% reported that they also have their own quality assurance program. Conclusions TDM of immunosuppressants is a recommended practice for transplant patients in Argentina. Initiatives need to be taken at the national level to develop uniform guidelines for analytical laboratories that include TDM-related quality assurance processes with regulatory force. There is also a need to train technical and professional personnel and to invite the participation of public and private organizations in the regulatory, public health, and research areas.

Characterization of mesenchymal stromal cells: potency assay development.

Based on their many different mechanisms of action, presumed immune-privileged status, and relative ease of production, mesenchymal stromal cells (MSCs) are under intensive clinical investigation for treating a wide range of degenerative, inflammatory, and immunologic disorders. Identification of relevant and robust potency assays is not only a regulatory requirement, but it is also the basis for producing and delivering a product that is consistent, safe, and ultimately an effective therapy. Although development of an appropriate potency assay is one of the most challenging issues in cell-based therapies, it is of paramount importance in the process of developing and testing cellular products. Regardless of the many different tissue sources and methods used in culture expansion of MSCs, they possess many of the same morphologic, cell surface markers, and differentiation characteristics. However, MSC products with similar phenotypic characteristics could still have major differences in their biologic and functional attributes. Understanding the different mechanisms of action and establishment of relevant potency assays is of pivotal importance in allowing investigators and regulatory agencies to compare MSCs used in different clinical trials.

Critical limits for urgent clinician notification at South African intensive care units.

BACKGROUND: Critical value policies are used by clinical laboratories to decide when to notify caregivers of life-threatening results. There, however, remains much debate regarding which tests should be included in critical value lists and clinically relevant limits. METHOD: An electronic survey was designed to determine the critical value policies of specialists for haematology tests in South African intensive care units. Data collected included a demographic component, critical value policies and critical value reporting. RESULTS: There were 68 respondents who represented a range of specialists from different disciplines. Four key critical values were identified, namely white cell count (WCC), haemoglobin, platelet count and international normalised ratio (INR). Median low and high adult and paediatric critical limits for the most frequently listed tests were as follows: haemoglobin <7 and >20 g/dL, platelet count <50 and >1000 × 10(9) /L, WCC < 2 and >20 × 10(9) /L and INR > 4. Specific critical limits for neonates were reported by 20 of the respondents. Of the respondents, 95.92% indicated that it was important to be contacted with first-time critical results and approximately half for repeat critical values. The majority preferred that the person notified of the critical value be the caregiver directly involved with the patient's care. CONCLUSION: It is important for critical value policies to be reviewed by each discipline to ensure cut-offs are clinically relevant.

[Safety in the Microbiology laboratory]. / Seguridad en el laboratorio de Microbiología Clínica.

The normal activity in the laboratory of microbiology poses different risks - mainly biological - that can affect the health of their workers, visitors and the community. Routine health examinations (surveillance and prevention), individual awareness of self-protection, hazard identification and risk assessment of laboratory procedures, the adoption of appropriate containment measures, and the use of conscientious microbiological techniques allow laboratory to be a safe place, as records of laboratory-acquired infections and accidents show. Training and information are the cornerstones for designing a comprehensive safety plan for the laboratory. In this article, the basic concepts and the theoretical background on laboratory safety are reviewed, including the main legal regulations. Moreover, practical guidelines are presented for each laboratory to design its own safety plan according its own particular characteristics.

[The metrological support of medical laboratory activity].

The article discusses the methodological approaches in implementing of regulations of the Federal law FZ-102 "On the support of unity of measurements in the area of laboratory medicine "from the positions of GOSTK ISO 9001-2008 "The systems of quality management. Requirements" and GOST K ISO 15189-2009 "medical laboratories. The particular requirements to quality and competence". The application of GOSTK ISO 18113.1-5 "The medicine items for diagnostic in vitro. Information provided by manufacturer (marking)" neatly assigns the responsibility for support of metrological correctness of laboratory measurements.

[Evaluation of schistocytes measurement guidelines]. / Évaluation de recommandations concernant l'identification et la numération des schizocytes : une enquête du Groupe francophone d'hématologie cellulaire.

The schistocytes are fragmented red blood cells mainly observed in the setting of hemolytic anemias and particularly among the thrombotic microangiopathies. The presence of schistocytes is an important criterion for the diagnosis of mechanical anemias, though the identification of these cells remains problematic. As a high variability of the morphologic identification criteria of the schistocytes among morphologists has been observed, some guidelines have been proposed after workshops (French and Italian groups). The International council for standardization in hematology published a consensus in November, 2011. The French group of cellular hematology (GFHC) aimed to recover the opinion of French biologists directly confronted to schistocytes measurements. 169 out 500 (34%) answered 10 questions dealing with the identification and measurements of schistocytes as proposed by the ICSH guidelines. A consensus was reached for the urgent need of guidelines documents, moreover in the current background of the European accreditation NF EN ISO 15189 rules. A traduction in native (French) language as warmly wished in order to facilitate the diffusion of the information. New fragmented red cell parameter recently provided by 2 manufacturers of automated blood cell counters remained doubtfull for routine use for half of the biologists.

[The practice of development and implementation of quality management systems in medical laboratories. The GOST R ISO 15189-2009 "medical laboratories. The detailed requirements to quality and competence". Particular difficulties of global nature].

The article discusses the methodological issues related to the implementation of international principles of standardization in the format of GOST R ISO 9001-2008 "Quality management systems. Requirements", GOST R ISO 15189-2009 "Medical laboratories. The detailed requirements to quality and competence" and GOST R ISO 18113.1-5 "Medical items for diagnostics in vitro. Information provided by manufacturer (marking)". This approach legibly assigns the responsibility concerning the support of metrological correctness of laboratory measurements. The lacking of both full-value public and sectorial normative documentation and coordinated positions of Rosstandard and Minzdrav of Russia on functioning of medical laboratories is noted.