我国良好实验室规范实施现状及发展

良好实验室规范（GLP）是一种规范的管理性文件。我国GLP的实施起步较晚,与发达国家相比还存在一定的差距。近年来,我国相关部门加大了管理力度,进一步完善了GLP体系。加强GLP实验室的管理,推行GLP检查和认证,有望推进国际安全性资料的互认,减少重复实验和资源浪费,降低研究成本。     

European Good Laboratory and Clinical Practices: their relevance to clinical pathology laboratories.

The requirements for Good Laboratory (GLP) and Good Clinical Practices (CGP) were established as a matter of urgency by the United States in the early 1970s. These were in response to gross misconduct and, in many instances, fraud. Over the next 15 years, a plethora of regulatory principles, guidelines, and regulations was produced by many countries of the world, culminating in single standards for European, Japanese, and United States authorities. Although with regard to GLP this has basically become a worldwide recognized standard within the preclinical (toxicology) studies, in the veterinary, chemical, agrochemical, and pharmaceutical industries, the GCPs are now seeing a rebirth. Within a clinical trials environment, there is most certainly a requirement for compliance with GCP, especially with regard to the harmonization of data within the European Community. The goal of this article is to cover the following aspects: Why should we have good practices? Why should laboratory data be audited? Why is there a need for a QA unit or function? What is the QA operational approach? How does a laboratory audit take place within laboratories? In discussing the laboratories and their subsequent data audits, the pitfalls and benefits are addressed and an examination of the data from the sponsor's viewpoint is compared with that produced by the laboratory. The types of laboratories present in a clinical environment are examined. They obviously comprise clinical pathology, microbiology, and analytical as well as ancillary hospital areas such as X-ray and cardiology. These laboratories may also be in the private sector, the National Health Service, contract laboratories, universities, or the general practitioner population.(ABSTRACT TRUNCATED AT 250 WORDS)     

Can non-regulators audit Independent Ethic Committees (IEC), and if so, how?

A number of guidelines and directives have reinforced the need for a more formalised approach to Independent Ethic Committees (IECs) and support the need to audit IECs. The key elements of an audit of an IEC are reviewed within the context of the European Guidelines for Auditing Independent Ethics Committees published by the European Forum for Good Clinical Practice (EFGCP). Auditing requirements in these recent guidelines and the EU Clinical Trial Directive are discussed as well as the methodology and type of documentation and SOPs that should be present at an audit. It is argued that both inspectorates and independent auditors need to conduct such audits to improve the overall global standard.     

Required steps for the validation of a Laboratory Information Management System.

The task of managing laboratory data is not a new one. Over the past two decades, the use of Laboratory Information Management Systems (LIMS) has revolutionized how laboratories manage their data. A LIMS is more than software; it has become the workhorse of the laboratory, encompassing laboratory work-flow combined with user input, data collection, instrument integration, data analysis, user notification, and delivery of information and reporting. Types of organizations that utilize LIMS vary greatly from research laboratories to manufacturing laboratories to environmental testing laboratories. Commercially-available LIMS have been around since the 1980s. In addition, many laboratories have designed, implemented, and maintained in-house LIMS. The heart of any LIMS is the software. Like other laboratory systems, the LIMS software is subject to quality control and quality assurance checks. In regulatory environments this associated QA/QC is referred to as "system validation." The primary purpose of system validation is to ensure that the software is performing in a manner for which it was designed. For example, the system acceptance criteria should be established and tested against quantifiable tasks to determine if the desired outcome has been achieved. LIMS features, such as autoreporting, reproducibility, throughput, and accuracy must be quantifiable and verifiable. System validation ensures that the entire system has been properly tested, incorporates required controls, and maintains and will continue to maintain data integrity. Laboratories must establish protocols and standards for the validation process and associated documentation. Although vendors of commercial LIMS perform initial internal system validations, the system must be revalidated whenever the end user, vendor or third party adds modifications or customizations to the LIMS. Currently, detailed guidance regarding system validation of LIMS is not available to the user. The issue is addressed in Good Automated Laboratory Practices (GALP) and National Environmental Laboratory Accreditation Conference (NELAC) documents which indicate specific requirements or recommendations for operational checks and periodic testing; however, it is up to the laboratory to determine suitable methods to accomplish these tasks. Proper validation of a LIMS will allow a laboratory to comply with regulations and also provide comprehensive documentation on the system that is necessary to troubleshoot future problems.     

Controlled trials of CQI and academic detailing to implement a clinical practice guideline for depression

BACKGROUND: The release of the Agency for Health Care Policy and Research (AHCPR)'s Guideline for the Detection and Treatment of Depression in Primary Care created an opportunity to evaluate under naturalistic conditions the effectiveness of two clinical practice guideline implementation methods: continuous quality improvement (CQI) and academic detailing. A study conducted in 1993-1994 at Kaiser Permanente Northwest Division, a large, not-for-profit prepaid group practice (group-model) HMO, tested the hypotheses that each method would increase the number of members receiving depression treatment and would relieve depressive symptoms. METHODS: Two trials were conducted simultaneously among adult primary care physicians, physician assistants, and nurse practitioners, using the same guideline document, measurement methods, and one-year follow-up period. The academic detailing trial was randomized at the clinician level. CQI was assigned to one of the setting's two geographic areas. To account for intraclinician correlation, both trials were evaluated using generalized equations analysis. RESULTS: Most of the CQI team's recommendations were not implemented. Academic detailing increased treatment rates, but--in a cohort of patients with probable chronic depressive disorder--it failed to improve symptoms and reduced measures of overall functional status. CONCLUSIONS: New organizational structures may be necessary before CQI teams and academic detailing can substantially change complex processes such as the primary care of depression. New research and treatment guidelines are needed to improve the management of persons with chronic or recurring major depressive disorder.     

《环境管理建立防治土地退化和荒漠化良好实践的指南第1部分:良好实践框架》国际标准分析研究

2017年10月,国际标准化组织ISO/TC 207环境管理标准化技术委员会正式发布了ISO 14055-1《环境管理建立防治土地退化和荒漠化良好实践的指南第1部分:良好实践框架》国际标准。本文对该项国际标准所提出的关键术语和定义、良好实践指南原则、确定造成土地退化和荒漠化的因素,以及建立良好实践并监测其实施等核心内容进行分析研究,旨在为我国土地退化和荒漠化防治与管理工作提供国际标准化经验和实践指引。     

The inspection of drug metabolism and pharmacokinetic studies.

Areas in which the regulations apply must be discussed to ensure that an overall standard of "good practice" is applied to Absorption Distribution Metabolism Excretion (ADME) as an integral part of the safety testing program. There are specific problems in adapting the toxicology regulations for drug metabolism and pharmacokinetic studies. In reviewing the laboratories and their experimental procedures, an attempt to identify, through an auditing approach, how a drug metabolism laboratory can comply with regulations is presented. It must be regarded as of paramount importance that all work be carried out to the highest standards to allow the largest margin of safety. With these experiences, ADME Laboratories "new" to Good Laboratory Practice can proceed along the compliance pathway with minimum trauma to man, animal, and machine.     

Proficiency Testing in Chemical Analysis of Iron Ore: Comparison of Statistical Methods for Outlier Rejection

Participation in proficiency testing (PT) is an important task to meet the requirements of ISO/IEC 17025 in the area of quality assurance of laboratory results. A PT program in the field of chemical analysis of iron ore was organized by CSIR-National Metallurgical Laboratory, Jamshedpur (nodal laboratory) and CSIR-National Physical Laboratory, New Delhi (PT Coordinator) during November 2011–January 2012. Twenty-two (22) laboratories in India participated in the PT program. The results of participating laboratories were first analyzed to identify the distribution patterns and the presence of outliers. Several parametric and robust statistical methods were used to identify the outliers. Correct outlier rejection is of utmost importance because the choice of the outlier test method influence the consensus value and standard deviation which in turn determine the Z-score of a laboratory result in a PT program. In the present study, five parametric outlier tests were compared: Dixon’s Q test, Grubbs single test, double test, t test, and Z-scores. In addition three robust tests as alternative to parametric tests were chosen: box plot, Huber test and MAD-based test. It was observed that multiple outlier test methods should be used to identify the outliers in a PT program especially when the number of participating laboratories is less. They complement each other and helps give diverse information and better overview of the data set. Among the 22 participating laboratories, Z-scores of 4 laboratories for analysis of total iron fall outside the acceptable limit of ±2. Similarly, for analysis of alumina and silica, five laboratories had unacceptable Z-scores.     

Ensuring safety of patients receiving sedation for procedures: evaluation of clinical practice guidelines

BACKGROUND: In 1995 The Johns Hopkins Hospital in Baltimore convened an interdisciplinary task force to evaluate sedation practices, create a comprehensive set of sedation guidelines, and evaluate patient safety outcomes following guideline implementation. METHODOLOGY: Baseline data were collected on all procedures in which sedation was administered by a nonanesthesiologist for a 6-month period, using scanning technology to automate data entry. Sedation practices were reviewed, and four critical events were examined: unresponsiveness, obstructed airway, airway placement, and cardiopulmonary resuscitation (CPR). In 1998 data collection procedures were repeated to evaluate the impact of the guidelines on sedation practices and patient safety outcomes. RESULTS: In 1995 sedation practices varied, and one or more critical events occurred in 45 (1.4%) of 3,255 procedures. Steps taken included development and dissemination of a clinical sedation guideline, including monitoring criteria to guide nonanesthesiologists, and evaluation planning. In 1998 sedation practices were more consistent. One or more critical events occurred in 50 (1.6%) of 3,134 procedures, representing a small increase in critical events from 1995. More events of unresponsiveness were identified, and no event required CPR. Although not statistically significant, this trend suggests that critical events were being identified earlier, preventing patients from progressing to a more serious event requiring CPR. Steps taken included further refinement of clinical practice guidelines and establishment of ongoing monitoring. CONCLUSIONS: Standardization of sedation practices is a complex and resource-intensive activity, requiring ongoing oversight and monitoring. Commitment from medical staff, nursing staff, and administration is essential to successful implementation of sedation guidelines.     

Findings and actions by the IR-4 Project in response to a bushel of EPA inspections.

The IR-4 Project is dedicated to all aspects of minor crop pest management, in cooperation between USDA, universities, and other state or Federal entities. Human safety decisions made by EPA are based upon field raw data, analytical reports, and scientific review and interpretation. Quality Assurance personnel, an independent body of internal inspectors and auditors, assist both regulatory inspector and on-site field personnel during EPA site inspections. This article contains information gleaned from a large number of university and other test site inspections, which were conducted by EPA to fulfill requirements of Good Laboratory Practice regulations, 40 CFR 160.     

The International Conference on Harmonization Good Clinical Practice guideline.

The purposes of the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guideline are to protect the rights of human subjects participating in clinical trials and to ensure the scientific validity and credibility of the data collected in human clinical studies. The guiding principle in the guideline is that the rights, safety, and well-being of the trial subject are the most important considerations and should prevail over the interests of science and society. The guideline will have an important and beneficial impact on the clinical trials conducted in the three participating regions (the United States, Europe, and Japan) as well as many other regions throughout the world. In the years to come, it should fulfill its intended purpose of providing for a more economical use of human, animal, and material resources and the elimination of unnecessary delays in the global development and availability of new medicines, and at the same time maintaining safeguards on quality, safety, and efficacy and regulatory obligations to protect public health.     

Best Practice Guidelines on Publishing Ethics: A Publisher's Perspective, 2nd Edition

Wiley has updated its publishing ethics guidelines, first published in 2006. These new guidelines provide guidance, resources, and practical advice on ethical concerns that arise in academic publishing for editors, authors, and researchers, among other audiences. New guidance is included about whistle blowers, animal research, clinical research, and clinical trial registration, addressing cultural differences, human rights, and confidentiality. The guidelines are uniquely interdisciplinary, and were reviewed by 24 editors and experts chosen from the wide range of communities that Wiley serves. These guidelines are also published in: Headache, International Journal of Clinical Practice, Annals of the New York Academy of Sciences, Social Science Quarterly, and on the website http://exchanges.wiley.com/ethicsguidelines .     

A comparison of the U.S. EPA FIFRA GLP standards with the U.S. FDA GLP standards for nonclinical laboratory studies.

In the early 1980's both the Environmental Protection Agency and the Food and Drug Administration were receiving studies on the products that they regulate that were unscientifically sound, some even being fraudulent. Studies were being submitted that had not been done under sound scientific practice; data were missing; necessary documentation to reconstruct the study, also known as an audit trail, was not in place, it was this evidence that lead to the Good Laboratory Practice Standards (GLPs) being codified and becoming regulation. The GLPs were meant to assure that studies submitted to the agencies for the registration of products for which they were responsible would protect the environment, and, the safety and health of the public.     

Prognostic implications of clinical practice guidelines among hemodialysis patients

Although the National Kidney Foundation (NKF) has published clinical practice guidelines for the management of risk factors for cardiovascular disease, these guidelines have not been tested rigorously for their effectiveness. We conducted an observational study among patients with end-stage kidney disease to examine the prognostic impact of threshold levels recommended by the NKF for blood pressure, hemoglobin, calcium-phosphate product, parathyroid hormone, low-density lipoprotein, and glycosylated hemoglobin. The study population (N = 197) was assembled from a previously completed randomized trial examining arteriovenous graft thrombosis. Cox proportional hazard analysis was used to calculate hazard ratios for the association of levels outside guideline recommended targets and death, adjusting for age, comorbidity, race, and albumin. The proportion of patients outside guideline targets ranged from 33% to 81%, and the impact of levels outside guideline targets on mortality varied substantially. Elevated calcium-phosphate product and glycosylated hemoglobin had harmful effects, with adjusted hazard ratios of 1.58 (95% CI 1.00-2.50; p = 0.050) and 2.21 (95% CI 0.99-4.97; p = 0.054), respectively. Nontarget levels for blood pressure, hemoglobin, and parathyroid hormone had little effect, with adjusted hazard ratios of 1.15 (95% CI 0.74-1.78; p = 0.542), 1.04 (95% CI 0.65-1.68; p = 0.866), and 0.90 (95% CI 0.50-1.61; p = 0.722), respectively. Elevated low-density lipoprotein had a paradoxically beneficial effect, with an adjusted hazard ratio of 0.48 (95% CI 0.23-1.00; p = 0.049). These results suggest that the prognostic impact of current threshold levels recommended by select NKF guidelines on mortality is variable. Accordingly, the development and implementation of clinical practice guidelines should be accompanied by corresponding efforts to confirm their impact on patient outcomes. Such efforts are essential for the improvement of guidelines and to inform health policy optimally.     

Flying test laboratory

Conclusions The organization of the measuring instruments' testing in situ is aimed at raising production quality.The experience of using flying test laboratories has confirmed the possibility of testing under utilization conditions even the most complicated radio-measuring instruments, thus ensuring an effective detection and withdrawal from operation of vital instruments whose technical characteristics do no meet specification requirements.Translated from Izmeritel'naya Tekhnika, No. 1, pp. 87–89, January, 1972.     

History of the Korean GLPs and the activities and perspectives of the Korean Society of GLP.

The Korean Society of Good Laboratory Practice (KSGLP) was established Dec. 10, 1998. The objectives of the KSGLP are to enhance the quality of domestic studies and the level of GLP compliance, in safety testing, and to promote information exchange among its members. The activities of KSGLP include: offering workshops and symposiums, linking with related governmental organizations, collecting GLP related information and providing the information to the related organizations, building international networks to collect information and to establish relationship, developing training materials and publishing periodicals, and other business necessary to achieve the objectives of the KSGLP. The KSGLP achieved its goals within a short period of time by offering workshops and symposia, and by providing important GLP related information in newspapers or via the KSGLP's internet homepage (www.ksglp.or.kr). The main role of the KSGLP will be to disseminate GLP technology nationwide. The KSGLP would like to help many labs that are preparing their facilities for GLP compliance. Further, the KSGLP is hoping to share GLP experiences with other members.     

Essentials of quality in "the gold standard veterinary clinical trial".

Quality Assurance (QA) has played a pivotal role within Good Laboratory Practice (GLP) since its inception in 1976. GLP is now recognized as a quality standard, as can be seen from the introductory statement of the recently issued OECD Principles of GLP (revised in 1997) that clearly state "GLP is a quality system concerned with the organisational process and the conditions under which non-clinical health and environmental safety studies are planned, performed, monitored, recorded, archived and reported". We can, therefore, see a close comparison between GLP compliance and the ISO/EN accreditation systems that have been adopted by other institutes on a worldwide basis.     

Comparison of an effect-model-law-based method versus traditional clinical practice guidelines for optimal treatment decision-making: application to statin treatment in the French population

Healthcare authorities make difficult decisions about how to spend limited budgets for interventions that guarantee the best cost-efficacy ratio. We propose a novel approach for treatment decision-making, OMES—in French: Objectif thérapeutique Modèle Effet Seuil (in English: Therapeutic Objective–Threshold–Effect Model; TOTEM). This approach takes into consideration results from clinical trials, adjusted for the patients'' characteristics in treatment decision-making. We compared OMES with the French clinical practice guidelines (CPGs) for the management of dyslipidemia with statin in a computer-generated realistic virtual population, representing the adult French population, in terms of the number of all-cause deaths avoided (number of avoided events: NAEs) under treatment and the individual absolute benefit. The total budget was fixed at the annual amount reimbursed by the French social security for statins. With the CPGs, the NAEs was 292 for an annual cost of 122.54 M€ compared with 443 with OMES. For a fixed NAEs, OMES reduced costs by 50% (60.53 M€ yr⁻¹). The results demonstrate that OMES is at least as good as, and even better than, the standard CPGs when applied to the same population. Hence the OMES approach is a practical, useful alternative which will help to overcome the limitations of treatment decision-making based uniquely on CPGs.     

Optical networks and laboratory services

Possible technical solutions to the problem of high speed data links between laboratories are presented. Long distance networks (WAN), ranging from tens to hundreds of kilometers, offer a variety of possibilities, from standard 64 Kbit/s connections to optical fiber links and radio or satellite Mbit channels. Short range (up to 2–3 km) communications are offered by many existing LAN (local area network) standards (e.g. Ethernet [1]) up to 10 Mbit/s. The medium distance range (around 10 km) can be covered by high performance fiber optic links and the now emerging MAN (metropolitan area network) protocols. A possible area of application is between the Gran Sasso Tunnel Laboratory, the outside installations and other Italian and foreign laboratories.