建立洁净区微生物数据库与无菌药品GMP生产过程控制的探讨

目的 建立洁净区微生物数据库,为追溯洁净区微生物污染来源提供依据,为无菌药品生产过程控制提供有力指导.方法 对乙型脑炎减毒活疫苗生产车间洁净区环境和操作人员进行微生物负载检测,并对该车间注射用水、纯化水系统样品进行微生物限度检测,鉴别研究相应分离菌,建立洁净区微生物数据库.同时对乙型脑炎减毒活疫苗中间产品进行无菌检查检测,并对阳性结果分离菌进行鉴别分析.然后根据建立的洁净区微生物数据库对阳性结果举例进行溯源探讨分析.结果 洁净区环境和人员主要存在里拉/藤黄微球菌、人葡萄球菌、表皮葡萄球菌以及科氏葡萄球菌科氏亚种等革兰阳性菌和蜡样芽胞杆菌等,水系统中则主要存在少动鞘氨醇单胞菌和铫子芽胞杆菌等.中间产品无菌阳性结果主要存在里拉/藤黄微球菌、蜡样芽胞杆菌以及奇异变形菌等,经调查分析,分别为操作过程中经环境偶然带入或试验动物操作不慎带入.结论 建立洁净区微生物数据库是追溯产品微生物污染来源的有效方法,能够为无菌药品GMP生产过程制定有效的控制措施提供依据,并使其更有针对性.     

质量保证体系的各个要素

随着药品生物制品企业质量管理工作的发展,特别是对ＧＭＰ的实施,质量保证（ＱＡ）逐渐成为生物制品企业的重要的质量管理体系。尽管ＱＣ和ＧＭＰ都是ＱＡ 的重要组成,但由于ＱＡ 作为特定的管理体系,在国内生物制品企业还始建不久,尚未形成适合本国企业的ＱＡ 理论体系,所以有必要结合国内外的经验开展ＱＡ 的理论研究,以有助于ＱＡ 工作的更有效的开展。本文对构成ＱＡ 体系中组织、计划、过程、因素、ＱＡ 方法等要素的内涵、相互关系以及与ＧＭＰ、ＱＣ、企业行政管理等外部要素的关系进行综述,旨在探讨ＱＡ 活动的规律性,以指导ＱＡ 的实践。     

在药品监管中建立近红外药品快速识别体系的分析及应用

近红外药品快速识别体系是医学界为了限制假药流入市场的一种重要措施,在药品监督工作中占有重要地位。本文从近红外药品快速识别体系的可行性入手,对近红外药品定性分析模型作详细分析,得出相关结论,供同行参考借鉴。     

药品生产环境中的新型自动监控系统

通过对药品生产环境重要性和保证生产环境的手段分析,介绍了一种新型的用于药品生产洁净室的自动监控方法,有效地保证了药品对生产环境的特殊要求。     

生物药品生产过程中污染问题的管控策略

生物药品制药流程严谨,每个步骤都需要达到对应的标准和规范,这是保证生物药品性能发挥的关键所在,也是其不同于其他生产行业的独特之处。文章从这个角度探究,探析生物药品生产过程中强化污染问题管理的必要性,对于生物药品生产过程中污染问题的管控,提出了建设性的意见和建议。     

试析药品生产风险管理存在问题归因分析及对策

本文分析了国内药品生产企业应用风险管理的现状,提出了实施质量风险管理的必要性,并指出在加强药品生产风险管理环节中应注意的几个问题,一是强化风险管理意识,二是建立信息反馈机制,三是进行评估与交流。     

关于药品生产工艺验证的新举措

在实施世界卫生组织（ＷＨＯ）和食品与药品管理局（ＦＤＡ）颁布的ＧＭＰ过程中,药品质量管理专家们发现单靠抽检样品不能反映市场上药品的实际质量,被抽检的样品结果合格,其同批药品的质量在事实上不一定符合标准。为此,他们经过多年的研究分析,应该对工艺过程的本身进行检验,即对生产工艺过程要进行验证,使ＧＭＰ概念深化到“质量保证”的新阶段     

探讨药品储存对药品质量的影响

影响药品质量的因素较多,由于药品的化学特性,在某些条件的影响下药品会出现水解、氧化、光化学分解、聚合以及变旋等化学反应,这些反应较为复杂,因此,药品的隔离保存与避光存存极为重要。     

High-precision quality assurance of robotic couches with six degrees of freedom

A robotic couch capable of six degrees of freedom (6-DoF) of motion was introduced for state-of-the-art radiation therapy. Patient treatment requires precise quality assurance (QA) of 6-DoF. Unfortunately, conventional methods do not provide the requisite accuracy and precision. Therefore, we developed a high-precision automated QA system using a visual tracking system (VTS). The VTS comprises four motion-sensing cameras, a cube with infrared reflective markers. To acquire data in treatment room coordinates, a transformation matrix from VTS coordinates to treatment room coordinates was determined.The mean error and standard deviation of linear and rotational motions, as well as couch sagging were analyzed from continuously acquired images in the moving couch. The accuracy of VTS was 0.024 mm deviation for the sinusoidal motion, and the accuracy of the transformation matrix was 0.02 mm. In a cross-comparison, the difference between Laser Tracker (FARO) measurements was 0.14 ± 0.12 mm for translation and 0.032 ± 0.026° on average for yaw rotation. The new system provides QA of yaw, pitch and roll motion as well as sagging of the couch and sub-millimeter/degree accuracy together with precision.     

TomoEQA: Dose verification for patient-specific quality assurance in helical tomotherapy using an exit detector

PurposeExisting phantom-less quality assurance (QA) platforms does not provide patient-specific QA for helical tomotherapy (HT). A new system, called TomoEQA, is presented to facilitate this using the leaf open time (LOT) of a binary multi-leaf collimator, as measured by an exit detector.MethodsTomoEQA was designed to provide measurement-based LOTs based on detector data and to generate a new digital imaging and communication in medicine (DICOM) dataset that includes the measured LOTs for use by secondary check platforms. To evaluate the system, 20 patient-specific QAs were performed using the program in Mobius3D software, and the results were compared to conventional phantom-based QA results.ResultsFrom our assessment, most of the differences between the planned and measured (or calculated) data, excluding one case, were within the acceptance criteria comparing with those of conventional QA. Regarding the gamma analysis, all results considered in this study were within the acceptance criteria. In addition, the developed system was performed for a failed case and showed approximately the same trends as the conventional approach.ConclusionsTomoEQA could perform patient-specific QAs of HT using Mobius3D and provide reliable patient-specific QAs results by evaluating point dose errors and 3D gamma passing rates. TomoEQA could also distinguish whether an intensity-modulated radiation therapy plan failed or not.     

Usefulness of a new online patient-specific quality assurance system for respiratory-gated radiotherapy

PurposeThe accuracy of gated irradiation may decrease when treatment is performed with short “beam-on” times. Also, the dose is subject to variation between treatment sessions if the respiratory rate is irregular. We therefore evaluated the impact of the differences between gated and non-gated treatment on doses using a new online quality assurance (QA) system for respiratory-gated radiotherapy.MethodsWe generated dose estimation models to associate dose and pulse information using a 0.6 cc Farmer chamber and our QA system. During gated irradiation with each of seven regular and irregular respiratory patterns, with the Farmer chamber readings as references, we evaluated our QA system’s accuracy. We then used the QA system to assess the impact of respiratory patterns on dose distribution for three lung and three liver radiotherapy plans. Gated and non-gated plans were generated and compared.ResultsThere was agreement within 1.7% between the ionization chamber and our system for several regular and irregular motion patterns. For dose distributions with measured errors, there were larger differences between gated and non-gated treatment for high-dose regions within the planned treatment volume (PTV). Compared with a non-gated plan, PTV D_95% for a gated plan decreased by −1.5% to −2.6%. Doses to organs at risk were similar with both plans.ConclusionsOur simple system estimated the radiation dose to the patient using only pulse information from the linac, even during irregular respiration. The quality of gated irradiation for each patient can be verified fraction by fraction.     

Clinically relevant quality assurance (QA) for prostate RapidArc plans: Gamma maps and DVH-based evaluation

The aim of this paper is to evaluate clinically relevant quality assurance (QA) tests for RapidArc prostate patients. 26 plans were verified by the COMPASS system that provides an independent angle response and a reconstruction of dose distribution in patient CT model. Plan data were imported from treatment planning system via DICOM. The fluencies, measured by a 2D detector, were used by COMPASS to forward calculate dose in CT patients and reconstruct dose-volume-histogram (DVH). The gamma analysis was performed, using both the criteria 3%-3-mm and 2%-2 mm, for the whole grid patient and the per-structure volume. A DVH-based analysis was accomplished for target and organs-at-risk (OAR). The correlation between gamma passing rates and DVH discrepancies was performed using Pearson's test. Sensitivity, specificity and accuracy of whole and per-structure gamma method were calculated.No significant DVH deviation was observed for target and OAR. Weak correlation between gamma passing rates and dosimetric deviations was observed, all significant r-values were negative. The whole gamma method shows lack of sensitivity to detect dosimetric deviations >5%. Instead, a better balance between sensitivity and specificity was obtained employing per structure gamma both with 3%-3 mm and 2%-2 mm criteria.Because of the poor correlation between DVH goals and gamma passing rates, we encourage the DVH-based gamma passing rates, when it is possible. At least, a gamma method specific for structure was strongly suggested.     

European guidelines for quality assurance in cervical cancer screening: recommendations for cervical cytology terminology

There are many different systems of cytology classification used in the member states of the European Union (EU) and many different languages. The following short annexe to Chapter 3 of the European Guidelines for Quality Assurance in Cervical Cancer Screening provides a framework that will allow different terminologies and languages to be translated into standard terminology based on the Bethesda system (TBS) for cytology while retaining the cervical intraepithelial neoplasia (CIN) classification for histology. This approach has followed extensive consultation with representatives of many countries and professional groups as well as a discussion forum published in Cytopathology (2005;16:113). This article will describe the reporting of specimen adequacy, which is dealt with in more detail elsewhere in Chapter 3 of the guidelines, the optional general categorization recommended in TBS, the interpretation/cytology result and other comments that may be made on reports such as concurrent human papillomavirus testing and the use of automation review and recommendations for management. The main categories in TBS will be described in the context of CIN, dyskaryosis and dysplasia terminologies so that all may be translated into the same framework. These guidelines should allow European countries to adapt their terminology in such a way as to make their screening programmes comparable with each other as well as with programmes elsewhere in the world.     

An institutional experience of quality assurance of a treatment planning system on photon beam

Aim

The purpose of the present study is to show the application of the IAEA TRS-430 QA procedures of Eclipse™v7.5 TPS for photon energies. In addition, the trends of the deviations found in the conducted tests were determined.

Background

In the past, the lack of complete TPS QA procedures led to some serious accidents. So, QA in the radiotherapy treatment planning process is essential for determination of accuracy in the radiotherapy process and avoidance of treatment errors.

Materials and methods

The calculations of TPS and measurements of irradiations of the treatment device were compared in the study. As a result, the local dose deviation values (δ₁: central beam axis, δ₂: penumbra and build up region, δ₃: inside field, δ₄: outside beam edges, δ_50–90: beam fringe, RW₅₀: radiological width) and their confidence limit values (including systematic and random errors) were obtained.

Results

The confidence limit values of δ₄ were detected to increase with expanding field size. The values of δ₁ and δ₃ of hard wedge were larger than open fields. The values of δ₂ and δ_50–90 of the inhomogeneity effect test were larger, especially than other tests of this study. The average deviation was showed to increase with the rise of the wedge angle. The values of δ₃ and δ₄ of lung irradiation were outside tolerance.

Conclusions

The QA of TPS was done and it was found that there were no reservations in its use in patient treatment. The trend of the deviations is shown.     

Internal quality assurance in cervical cytology—one laboratory's experience

The results of an internal quality assurance exercise in one cervical cytology laboratory in England are presented, using differing types of partial percentage re-screening of cervical smears. An overall false-negative dyskaryotic rate of up to 4.3% was demonstrated, with the final cytology report diagnosis differing from the primary screening diagnosis in 1.3% of cases. These findings are discussed, with the aim of helping to foster debate on the setting of national laboratory internal quality assurance standards.     

Rapid pre-screening: a validated quality assurance measure in cervical cytology

We present the results of 3 years' experience of rapid pre-screening in cervical cytology. In our laboratory we rapidly pre-screen all smears. The performance of each primary screener can be assessed. In addition, the relative sensitivity and specificity of each rapid pre-screener can itself be continuously monitored using the final report as a yardstick. In our laboratory individual sensitivity of rapid pre-screening for the detection of high-grade abnormalities was in the range of 44-90% with an overall laboratory sensitivity of 69%. Specificity was in the range of 94-99% with an overall laboratory specificity of 98%. Rapid pre-screening allows checking of the checkers and pathologists and tends to promote uniformity in the assessment of smear adequacy. This form of continuous quality assurance is practical, convenient and acceptable to staff.     

Evaluations of a flat-panel based compact daily quality assurance device for proton pencil beam scanning (PBS) system

PurposeTo evaluate the flat-panel detector quenching effect and clinical usability of a flat-panel based compact QA device for PBS daily constancy measurements.Materials & MethodThe QA device, named Sphinx Compact, is composed of a 20x20 cm² flat-panel imager mounted on a portable frame with removable plastic modules for constancy checks of proton energy (100 MeV, 150 MeV, 200 MeV), Spread-Out-Bragg-Peak (SOBP) profile, and machine output. The potential quenching effect of the flat-panel detector was evaluated. Daily PBS QA tests of X-ray/proton isocenter coincidence, the constancy of proton spot position and sigma as well as the energy of pristine proton beam, and the flatness of SOBP proton beam through the 'transformed' profile were performed and analyzed. Furthermore, the sensitivity of detecting energy changes of pristine proton beam was also evaluated.ResultsThe quenching effect was observed at depths near the pristine peak regions. The flat-panel measured range of the distal 80% is within 0.9 mm to the defined ranges of the delivered proton beams. X-ray/proton isocenter coincidence tests demonstrated maximum mismatch of 0.3 mm between the two isocenters. The device can detect 0.1 mm change of spot position and 0.1 MeV energy changes of pristine proton beams. The measured transformed SOBP beam profile through the wedge module rendered as flat.ConclusionsEven though the flat-panel detector exhibited quenching effect at the Bragg peak region, the proton range can still be accurately measured. The device can fulfill the requirements of the daily QA tests recommended by the AAPM TG224 Report.