ISO 15189 is a sufficient instrument to guarantee high-quality manufacture of laboratory developed tests for in-house-use conform requirements of the European In-Vitro-Diagnostics Regulation.

The EU In-Vitro Diagnostic Device Regulation (IVDR) aims for transparent risk-and purpose-based validation of diagnostic devices, traceability of results to uniquely identified devices, and post-market surveillance. The IVDR regulates design, manufacture and putting into use of devices, but not medical services using these devices. In the absence of suitable commercial devices, the laboratory can resort to laboratory-developed tests (LDT) for in-house use. Documentary obligations (IVDR Art 5.5), the performance and safety specifications of ANNEX I, and development and manufacture under an ISO 15189-equivalent quality system apply. LDTs serve specific clinical needs, often for low volume niche applications, or correspond to the translational phase of new tests and treatments, often extremely relevant for patient care. As some commercial tests may disappear with the IVDR roll-out, many will require urgent LDT replacement. The workload will also depend on which modifications to commercial tests turns them into an LDT, and on how national legislators and competent authorities (CA) will handle new competences and responsibilities. We discuss appropriate interpretation of ISO 15189 to cover IVDR requirements. Selected cases illustrate LDT implementation covering medical needs with commensurate management of risk emanating from intended use and/or design of devices. Unintended collateral damage of the IVDR comprises loss of non-profitable niche applications, increases of costs and wasted resources, and migration of innovative research to more cost-efficient environments. Taking into account local specifics, the legislative framework should reduce the burden on and associated opportunity costs for the health care system, by making diligent use of existing frameworks.

In vitro fertilization and andrology laboratory in 2030: expert visions.

The aim of this article is to gather 9 thought leaders and their team members to present their ideas about the future of in vitro fertilization and the andrology laboratory. Although we have seen much progress and innovation in the laboratory over the years, there is still much to come, and this article looks at what these leaders think will be important in the future development of technology and processes in the laboratory.

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.

Testing For SARS-CoV-2: The Day the World Turned its Attention to the Clinical Laboratory.

In the last few months, an unprecedented number of laboratory tests for coronavirus disease 2019 (COVID-19) have been developed at a remarkable speed. With the rapid adoption of these tests into clinical practice, combined with the widespread publicity they received, questions arose related to the different types of tests, their utility, performance, and regulatory approval status. The aim of this publication is to provide a general landscape of laboratory testing for COVID-19 and offer a historical and regulatory perspective associated with them. Specifically, we aim to elaborate on the regulatory complexities of diagnostic testing in the United States and its implications to the present outbreak, as well as provide a synopsis of laboratory tests that have been developed for COVID-19. We will first address the detection of severe acute respiratory syndrome-coronavirus 2 directly by either nucleic acid amplification tests or by the detection of the viral protein for active infections. Subsequently, we will provide an overview of serological tests that can aid not only in diagnosis but additionally help to identify prior infections and potential immunity.

[Patient-initiated diagnostics - a challenge for laboratory medicine]. / Egenordinerad provtagning kan ge laboratoriemedicinen ny roll.

Citizens can now order their own laboratory investigations. Self-testing is in line with increasing patient empowerment and in conflict with existing routines in medicine where all tests are ordered by the physician. Several challenges have to be faced by laboratory medicine to secure the quality and increase the medical benefits of patient-initiated diagnostics.

The New, New Daptomycin Breakpoint for Enterococcus spp.

In 2019, the Clinical and Laboratory Standards Institute revised the daptomycin breakpoints for Enterococcus spp. twice in rapid succession. Analyses leading to these revisions included review of testing issues, murine and human in vivo pharmacodynamics, safety of off-label doses, and treatment outcomes. The data review brought up a dilemma that is encountered with increasing frequency: a breakpoint supported by pharmacokinetic/pharmacodynamic modeling that bisected the wild-type Enterococcus faecium MIC distribution. In such instances, not only does the probability of pharmacokinetic/pharmacodynamic targets need to be taken into account but also the probability that the laboratory can generate an accurate MIC that is reproducible within one interpretive category.

Understanding and Addressing CLSI Breakpoint Revisions: a Primer for Clinical Laboratories.

The Clinical and Laboratory Standards Institute (CLSI) has revised several breakpoints since 2010 for bacteria that grow aerobically. In 2019, these revisions include changes to the ciprofloxacin and levofloxacin breakpoints for the Enterobacteriaceae and Pseudomonas aeruginosa, daptomycin breakpoints for Enterococcus spp., and ceftaroline breakpoints for Staphylococcus aureus Implementation of the revisions is a challenge for all laboratories, as not all systems have FDA clearance for the revised (current) breakpoints, compounded by the need for laboratories to perform validation studies and to make updates to laboratory information system/electronic medical record builds in the setting of limited information technology infrastructure. This minireview describes the breakpoint revisions in the M100 supplement since 2010 and strategies for the laboratory on how to best adopt these in clinical testing.

Facing the Inevitable: Being Prepared for Regulatory Requirements for Laboratory Developed Tests.

OBJECTIVES: We introduce regulatory terms, definitions, and the Quality System Regulation as proposed by the US Food and Drug Administration in the 2014 draft guidance entitled Framework for Regulatory Oversight of Laboratory Developed Tests and explore medical device requirements applicable to a laboratory environment to design, develop, and validate laboratory developed tests (LDTs). METHODS: We performed nine interviews with laboratory professionals to explore concerns and challenges regarding the draft, translated the results into operational factors, and surveyed professionals to test the factors that would comprise a regulatory quality management system framework. RESULTS: Nine interviewees and 35 survey respondents shared concerns of risk classification, process validation, patient safety, and general ambiguity regarding the proposed requirements for development of LDTs. CONCLUSIONS: Respondents agree that a regulatory quality management system is needed in laboratories that develop LDTs, but the translation and method for design control to a clinical laboratory do not exist. As a result, laboratories are taking the wait-and-see approach.

Delivering modern, high-quality, affordable pathology and laboratory medicine to low-income and middle-income countries: a call to action.

Modern, affordable pathology and laboratory medicine (PALM) systems are essential to achieve the 2030 Sustainable Development Goals for health in low-income and middle-income countries (LMICs). In this last in a Series of three papers about PALM in LMICs, we discuss the policy environment and emphasise three crucial high-level actions that are needed to deliver universal health coverage. First, nations need national strategic laboratory plans; second, these plans require adequate financing for implementation; and last, pathologists themselves need to take on leadership roles to advocate for the centrality of PALM to achieve the Sustainable Development Goals for health. The national strategic laboratory plan should deliver a tiered, networked laboratory system as a central element. Appropriate financing should be provided, at a level of at least 4% of health expenditure. Financing of new technologies such as molecular diagnostics is challenging for LMICs, even though many of these tests are cost-effective. Point-of-care testing can substantially reduce test-reporting time, but this benefit must be balanced with higher costs. Our research analysis highlights a considerable deficiency in advocacy for PALM; pathologists have been invisible in national and international health discourse and leadership. Embedding PALM in LMICs can only be achieved if pathologists advocate for these services, and undertake leadership roles, both nationally and internationally. We articulate eight key recommendations to address the current barriers identified in this Series and issue a call to action for all stakeholders to come together in a global alliance to ensure the effective provision of PALM services in resource-limited settings.

Clinical Laboratory Improvement Amendments of 1988 (CLIA); Fecal Occult Blood (FOB) Testing. Final rule.

This final rule amends the Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulations to clarify that the waived test categorization applies only to non-automated fecal occult blood tests.

Laboratory-Developed Tests: A Legislative and Regulatory Review.

BACKGROUND: Twenty-five years ago, the Food and Drug Administration (FDA) asserted in a draft document that "home brew" tests-now commonly referred to as laboratory-developed tests (LDTs)-are subject to the same regulatory oversight as other in vitro diagnostics (IVDs)4. In 2010, the FDA began work on developing a proposed framework for future LDT oversight. Released in 2014, the draft guidance sparked an intense debate over potential LDT regulation. While the proposed guidance has not been implemented, many questions regarding LDT oversight remain unresolved. CONTENT: This review provides an overview of federal statutes and regulations related to IVDs and clinical laboratory operations, with a focus on those potentially applicable to LDTs and proposed regulatory efforts. Sources reviewed include the Code of Federal Regulations, the Federal Register, congressional hearings, guidance and policy documents, position statements, published literature, and websites. SUMMARY: Federal statutes regarding IVDs were passed without substantive evidence of congressional consideration toward the concept of LDTs. The FDA has clear oversight authority over IVD reagents introduced into interstate commerce. A 16-year delay in publicly asserting FDA authority over LDTs, the pursuit of a draft guidance approach toward oversight, and establishment of regulations under the Clinical Laboratory Improvement Amendments of 1988 (CLIA'88) applicable to LDTs contributed to community uncertainty toward LDT oversight. Future regulatory and/or legislative efforts may be required to resolve this uncertainty.

Considerations of developing an NGS assay for clinical applications in precision oncology: The NCI-MATCH NGS assay experience.

Next generation sequencing (NGS) technologies have been widely adapted in clinical oncology by utilizing the profiled genetic mutation information to select patients and to guide the choice of target therapy. To fulfill the regulatory compliance, development of an NGS assay that will be used in clinical trials requires an analytical validation to meet its intend clinical use. NCI-MATCH trial is the largest precision oncology basket trial which uses a single NGS assay (NCI-MATHC NGS assay) to screen the actionable mutations in 6000 patients, who have relapsed/refractory solid tumors and lymphomas after standard systemic treatment, and assigns matched treatment. This article reviews on the critical considerations during development and validation of NGS assays as an investigational device for genomic based clinical trials and provides the experiences from the development of NCI-MATCH NGS assay.

Procedimiento para la transferencia y revisión de intervalos de referencia biológicos / Procedure for transference and review of biological reference intervals

No disponible

Return of experience on the initial audit of Cofrac and projects for the release of results of emergency biological tests.

Legislation and ISO 15189 international standard provide that the clinical laboratories shall organize the communication of the biological assay results, especially with the establishment of a list of critical assays, whose results shall be reported during doctor's on call period but also through restricting result transmission to biologically validated results. Actually continuous validation and immediate procession of the medical records belonging to patients in emergency situation are not always possible, because of the biologist's workload and the other activities he is responsible for. Based on the modified version of SH REF 04, we intend to export on the servers the results of critical assays during both the day time and doctor's on call period, as they are validated by the authorized technician, under the responsibility of the biologist in charge of validation. With this project, it will be possible at the same time to respond to the clinical requirements, and, for the biologist, to perform all his functions that are important to ensure the smooth running and the development of the laboratory.

Understanding the Food and Drug Administration's Jurisdiction Over Laboratory-Developed Tests and Divisions Between Food, Drug, and Cosmetic Act-Regulated and Clinical Laboratory Improvement Amendments of 1988-Regulated Activities.

The scope of FDA's jurisdiction over laboratory-developed tests (LDTs), and whether FDA has such jurisdiction at all, has been a heavily debated issue over the past several years. If FDA moves forward with its guidance, or Congress takes action to reform LDT and IVD regulation, a fundamental question that needs to be answered is how to divide activities regulated by FDCA from those regulated by CLIA. In this article, we consider FDA's authority to regulate LDTs and the policy implications of regulation, and discuss an idea for a fact-driven framework to distinguish FDCA- and CLIA- activities.