Volume 36, Issue 6

The 4th amendment of the German Act on Medical Devices became effective on the 21st March 2010. With this amendment, a mandatory recognition by the competent authority was established for certain laboratories to determine their expertise. This article describes the basics of the recognition as well as the similarities and differences regarding the accreditation of laboratories in the area of medical devices. The requirements for recognition and accreditation of laboratories in the area of medical devices are equal in content. Furthermore, in both procedures, the assessment is conducted by the competent authority. Thus, there are synergies in concurrent recognition and accreditation, even if the recognition is not always mandatory but often advantageous.

The new draft of the international standard ISO/DIS 15189:2011 “Medical laboratories – Specific requirements for quality and competence” sets substantially extended requirements for the quality management system of medical laboratories. The changes may be differentiated into three categories: editorial, structural and contents. Essential criteria of this standard, which is intended to be also applied for accreditation purposes, are related to novel management and technical requirements. In the center of the quality management documentation, the future standard not only requires a quality manual but also a set of more than 20 mandatory “documented procedures”. For the subcontracting of referral laboratories, the draft standard contains a clear obligation for identification of the subcontractors which will increase overall transparency for patients and other laboratory users. Concepts for risk management and extended review activities are newly introduced into the draft standard. Key aspects of the technical requirements are related to the specification of criteria for validation and verification of examination procedures and to the quality assurance of examination results. The new draft standard requires – according to the current state of the art – compliance with selected quality criteria for report validation and the laboratory information management system. In a regulatory context, the ISO/DIS 15189:2011 is related to the current revision of the European medical device legislation, which – among others – covers in vitro diagnostic medical devices and which will be implemented by the national medical device act.

Benchmarking is a systematic and continuous process to compare products, services, and processes – in quantitative and qualitative aspects. Benchmarking in laboratory medicine departments of hospitals is a frequently used but only poorly standardized method. Sophisticated procedures for data collection are necessary due to large heterogeneity and complexity of activities performed in laboratory medicine with regard to type of testing, response times, availability and amount of different resources needed for single analysis and reporting. These prerequisites are difficult to fulfill. In internal benchmarking projects – i.e., monitoring of productivity, costs, and revenues within one laboratory over an extended period of time – the current tools for data collection are generally suited for use. In external benchmarking, however, several pitfalls may obscure the results. Broadly, external benchmarking projects compare only partial processes with sufficient validity. Differences in benchmarking have to be controlled for improvements of data collection and for changes of surrounding conditions outside the laboratory. This review lists different approaches for benchmarking projects in laboratory medicine departments and describes their strengths and weaknesses.

Benchmarking is a systematic and continuous process used to compare products, services, and processes – as regards quantitative and qualitative aspects. Benchmarking in laboratory medicine departments of hospitals is a frequently used but only poorly standardized system. Sophisticated procedures for data collection are necessary due to the large heterogeneity and complexity of activities performed in laboratory medicine with regard to the type of testing, response times, availability and amount of different resources needed for single analysis and reporting. These prerequisites are difficult to fulfill. In internal benchmarking projects – i.e., monitoring of productivity, costs, and revenues within one laboratory over an extended period of time – the current tools for data collection are generally fit for purpose. In external benchmarking, however, several pitfalls may obscure the results. In broad terms, external benchmarking projects compare only partial processes with sufficient validity. Differences in benchmarking have to be controlled for improvements of data collection and for changes in surrounding conditions outside the laboratory. This review lists different approaches for benchmarking projects in laboratory medicine departments and describes their strengths and weaknesses.

Owing to the huge demographic challenge in terms of a considerable restructuring of the employed workforce, hospital care has changed and thus laboratory medicine underlies increased rationalization pressure. Management solutions include internal process optimization, procurement management, service outsourcing and development of regional networks. Laboratory medicine must realize these solutions, particularly with reference to quality assurance, to remain competitive in the future.

Owing to the huge demographic challenge in terms of a considerable restructuring of the employed workforce, hospital care has changed and thus laboratory medicine underlies increased rationalization pressure. Management solutions include internal process optimization, procurement management, service outsourcing and development of regional networks. The laboratory medicine must face these challenges in order to remain competitive.

Background: Natalizumab (Tysabri) is a blocking antibody specific for the α-4 integrin subunit and can be detected on the surface of immune cells by flow cytometry. We investigated if determination of natalizumab saturation of immune cells has the potential to act as a biomarker for treatment effectiveness in multiple sclerosis (MS). Methods: Natalizumab saturation of immune cells from 11 patients was measured before the start of treatment and after 4, 8, and 12 weeks of natalizumab therapy on T cells (CD3 + ) and T cell subsets [naive (CD45RA + /memory (CD45R0 + ) CD4 + and CD8 + ] by flow cytometry. Results: At weeks 4, 8, and 12 the average (n=9) natalizumab saturation of T cells approximated 80%. One patient with natalizumab neutralizing antibodies (NABs) and another patient with irregular infusion intervals were identified by abnormalities in the natalizumab saturation of cells. Different α-4 expression levels of T cell subpopulations were irrelevant to measuring cellular natalizumab saturation. Conclusions: We show that monitoring natalizumab saturation of T cells by flow cytometry is a useful and routine-qualified method to identify patients with a reduced treatment effect due to NABs or irregular infusion intervals. Further studies to determine a cut-off value for suboptimal natalizumab saturation of immune cells will also show the potential of this parameter concerning more individualized treatment schedules. Considering the risk of opportunistic infections, it is very important to increase the safety of this highly effective MS therapy.

Background: Natalizumab (Tysabri) is a blocking antibody specific to the α-4 integrin subunit and can be detected on the surface of immune cells by flow cytometry. We investigated if the determination of natalizumab saturation of immune cells has the potential to act as a biomarker for treatment effectiveness in multiple sclerosis (MS). Methods: Natalizumab saturation of immune cells from 11 patients was measured before the start of treatment and after 4, 8, and 12 weeks of natalizumab therapy on T cells (CD3 + ) and T cell subsets [naive (CD45RA + /memory (CD45R0 + ) CD4 + and CD8 + ] by flow cytometry. Results: At weeks 4, 8, and 12 the average (n=9) natalizumab saturation of T cells approximated 80%. One patient with natalizumab neutralizing antibodies (NABs) and another patient with irregular infusion intervals were identified by abnormalities in the natalizumab saturation of cells. Different α-4 expression levels of T cell subpopulations were irrelevant to measuring cellular natalizumab saturation. Conclusions: We showed that monitoring natalizumab saturation of T cells by flow cytometry is a useful and routine-qualified method to identify patients with a reduced treatment effect due to NABs or irregular infusion intervals. Further studies to determine a cut-off value for suboptimal natalizumab saturation of immune cells will also show the potential of this parameter concerning more individualized treatment schedules. Considering the risk of opportunistic infections it is very important to increase the safety of this highly effective MS therapy.

During the past years treatment of multiple sclerosis (MS) has critically improved with the introduction of new and very effective drugs. These modern MS therapeutics selectively interfere with immune cell trafficking resulting in substantial shifts in leukocyte counts in peripheral blood. Strikingly, investigations of cerebrospinal fluid (CSF) also revealed immunological changes behind the blood-CSF barrier which might contribute to the increased effectiveness of these drugs. By contrast, these changes might account for a reduced immune surveillance of the central nervous system (CNS) and favor the occurrence of opportunistic infections such as progressive multifocal leukoencephalopathy. In this review, we focus on immunological changes induced by two approved agents in the treatment of highly active MS, natalizumab and fingolimod, and outline the current knowledge about their impact in the CSF compartment of the CNS. Further investigations and monitoring of immunological changes in CSF under MS therapy might help to provide further information about immunological changes.

The introduction of several new therapies for the treatment of multiple sclerosis (MS) has improved the situation of many MS patients. However, the spectrum of potential side effects in MS treatment has also become broader with the introduction of the new therapeutics. Thus, innovative and, in the meantime, well-established laboratory parameters have been introduced for routine testing to improve efficacy and side effects, and therefore the quality of immune treatment regimens. We provide an overview on important aspects of MS treatment and pathogenesis. We then present therapy-specific laboratory parameters of the most important disease-modifying substances. Some have only recently been established and they also have the potential to be in disarray, leading to confusion and insufficient results. Appropriate use of the presented biomarkers is therefore essential and will improve safety in the handling of MS-specific substances.

A variety of methods are available for virological diagnosis and immunity assessment of influenza. For virus detection, the clinical specimen is usually the respiratory swab. In terms of sensitivity, nasopharyngeal aspirates are superior and sputum specimens are inferior. The diagnostic method of choice is RT-PCR of viral DNA sequences coding for matrix and nucleoprotein, which define influenza virus types A, B, C, or coding for haemagglutinin and neuraminidase spikes on the viral envelope identifying influenza virus A subtypes and strains. Gene-specific primer probes are commercially available. PCR takes 1–2 h after the arrival of the clinical specimen. Cell culture based virus isolation combined with intracellular antigen detection needs 1–2 days, but is regarded as gold standard. Transport of the swabs in an ice chest is recommendable. Direct antigen detection in the clinical specimen by the use of enzyme-linked immunosorbent assay (ELISA) or immunofluorescence test (IFT) is the most rapid (bedside) method, but of inferior sensitivity. Therapy resistance analysis is done by genotyping subsequent to PCR amplification or by the cell culture method (phenotyping). Antibodies due to influenza virus are produced during the second week after infection and may confirm or disprove virological diagnosis. ELISA and IFT apply nucleoprotein or matrix proteins as antigens and differentiate between the Ig classes IgA (IgM) and IgG indicating an acute or passed infection. Complement fixing antibodies do not persist. Influenza virus immunity is assessed by neutralisation assay or – more simply – by haemagglutination inhibition in a type-, subtype- and even variant-specific manner.

A variety of methods are available for virological diagnosis and immunity assessment of influenza. For virus detection, the clinical specimen is usually the respiratory swab. In terms of sensitivity, nasopharyngeal aspirates are superior and sputum specimens are inferior. The diagnostic method of choice is RT-PCR of viral DNA sequences coding for matrix and nucleoprotein, which define influenza virus types A, B, C, or coding for hemagglutinin and neuraminidase spikes on the viral envelope identifying influenza virus A subtypes and strains. Genespecific primer probes are commercially available. PCR takes 1–2 h after the arrival of the clinical specimen. Cell culture based virus isolation combined with intracellular antigen detection needs 1–2 days, but is regarded as gold standard. Transport of the swabs in an ice chest is recommendable. Direct antigen detection in the clinical specimen by the use of enzyme-linked immunosorbent assay (ELISA) or immunofluorescence test (IFT) is the most rapid (bedside) method, but of inferior sensitivity. Therapy resistance analysis is done by genotyping subsequent to PCR amplification or by the cell culture method (phenotyping). Antibodies due to influenza virus are produced during the second week after infection and may confirm or disprove virological diagnosis. ELISA and IFT apply nucleoprotein or matrix proteins as antigens and differentiate between the Ig classes IgA (IgM) and IgG indicating an acute or passed infection. Complement fixing antibodies do not persist. Influenza virus immunity is assessed by neutralization assay or – more simply – by hemagglutination inhibition in a type-, subtype- and even variantspecific manner.

Chronic myeloid leukemia is a neoplastic disorder of hematopoiesis characterized by the BCR-ABL1 fusion gene. Three selective tyrosine kinase inhibitors are approved for the treatment of de novo patients. Early and regular molecular monitoring is essential to assess residual disease. It allows for early prognosis predictions and an early detection of a relapse or resistance to therapy. Harmonization of the detection method and laboratory report is important for assessment of the therapeutic response. A rapid delivery of laboratory reports motivates patients to compliance. The following report by a German panel of experts discusses recommendations for harmonization of the detection method and laboratory report.