基于FMEA的C形臂X线机的使用风险分析与控制

??????? 目的 基于失效模式与效应分析（FMEA）方法分析控制C形臂X线机的使用风险。方法 成立FMEA 5人小组,运用现场观察和访谈的方法,识别C形臂X线机使用的潜在失效模式,并对其发生的严重度、发生概率及检测的难易度进行评价打分,计算失效原因的风险优先指数。结果 FMEA小组找出了必须优先解决的C臂机使用的失效模式,制定并实施了改进措施,在不增加管理成本的基础上,取得了良好的管理效果。结论 FMEA可以评估医疗设备使用过程的失效,并能排序优先解决的问题,不增加管理成本就能预防问题的发生,是有效的过程管理工具。     

基于失效模式与效应分析法的临床药学服务风险研究

目的 探讨临床药学服务过程中的风险及引起风险的主要原因,通过一定的方式规避风险。方法 应用失效模式与效应分析法对临床药学服务模式进行风险识别管理和研究。结果 分析得出临床药学服务模式共计15项流程,21项失效环节,对其中排名靠前的高危风险提出了相应的干预措施。结论 失效模式与效应分析法可以前瞻地有效地识别高危风险,并结合风险产生的原因,针对性地采取干预措施,从而最大程度地规避风险的发生。     

失效模式与效应分析在化疗药物安全输注中的应用

目的运用失效模式与效应分析（FMEA）降低化疗药物输注过程中的风险,保证输注安全。方法根据FMEA方法,成立项目小组;制定操作流程图,进行失效模式与潜在风险原因分析,计算优先风险指数（RPN）;找出失效模式及原因;进行措施改进。结果 2012年1~5月与前年同期比较,化疗药物外渗和静脉炎的发生率差异有统计学意义（0.1%vs 0.6%;0.6%vs 1.5%,P〈0.05）。结论 FMEA应用于化疗患者,能显著降低静脉炎和药物外渗发生的风险,保证患者安全。     

Management of externally manufactured cell therapy products: the Mayo Clinic approach

BackgroundThe rise of investigative and commercially available cell therapy products adds a new dynamic to academic medical centers; that is, the management of patient-specific cell products. The scope of cell therapy has rapidly expanded beyond in-house collection and infusion of cell products such as bone marrow and peripheral blood transplant. The complexities and volumes of cell therapies are likely to continue to become more demanding. As patient-specific “living drugs,” cell therapy products typically require material collection, product provenance, transportation and maintenance of critical quality attributes, including temperature and expiration dates. These requirements are complicated by variations in product-specific attributes, reporting requirements and interactions with industry not required of typical pharmaceuticals.MethodsTo manage these requirements, the authors set out to establish a framework within the Immune, Progenitor and Cell Therapeutics Lab, the Current Good Manufacturing Practice facility responsible for cell manufacturing at Mayo Clinic Rochester housed within the Division of Transfusion Medicine. The authors created a work unit (biopharmaceutical unit) dedicated to addressing the specialized procedures required to properly handle these living drugs from collection to delivery and housing the necessary processes to more easily integrate externally manufactured cell therapies into clinical practice.ResultsThe result is a clear set of expectations defined for each step of the process, with logical documentation of critical steps that are concise and easy to follow.ConclusionsThe authors believe this system is scalable for addressing the promised growth of cell therapy products well into the future. Here the authors describe this system and provide a framework that could be used by other centers to manage these important new therapies.     

A Systematic Approach of Employing Quality by Design Principles: Risk Assessment and Design of Experiments to Demonstrate Process Understanding and Identify the Critical Process Parameters for Coating of the Ethylcellulose Pseudolatex Dispersion Using Non-Conventional Fluid Bed Process

The goal of this study was to utilize risk assessment techniques and statistical design of experiments (DoE) to gain process understanding and to identify critical process parameters for the manufacture of controlled release multiparticulate beads using a novel disk-jet fluid bed technology. The material attributes and process parameters were systematically assessed using the Ishikawa fish bone diagram and failure mode and effect analysis (FMEA) risk assessment methods. The high risk attributes identified by the FMEA analysis were further explored using resolution V fractional factorial design. To gain an understanding of the processing parameters, a resolution V fractional factorial study was conducted. Using knowledge gained from the resolution V study, a resolution IV fractional factorial study was conducted; the purpose of this IV study was to identify the critical process parameters (CPP) that impact the critical quality attributes and understand the influence of these parameters on film formation. For both studies, the microclimate, atomization pressure, inlet air volume, product temperature (during spraying and curing), curing time, and percent solids in the coating solutions were studied. The responses evaluated were percent agglomeration, percent fines, percent yield, bead aspect ratio, median particle size diameter (d50), assay, and drug release rate. Pyrobuttons® were used to record real-time temperature and humidity changes in the fluid bed. The risk assessment methods and process analytical tools helped to understand the novel disk-jet technology and to systematically develop models of the coating process parameters like process efficiency and the extent of curing during the coating process.     

Quality by Design I: Application of Failure Mode Effect Analysis (FMEA) and Plackett–Burman Design of Experiments in the Identification of “Main Factors” in the Formulation and Process Design Space for Roller-Compacted Ciprofloxacin Hydrochloride Immediate-Release Tablets

As outlined in the ICH Q8(R2) guidance, identifying the critical quality attributes (CQA) is a crucial part of dosage form development; however, the number of possible formulation and processing factors that could influence the manufacturing of a pharmaceutical dosage form is enormous obviating formal study of all possible parameters and their interactions. Thus, the objective of this study is to examine how quality risk management can be used to prioritize the number of experiments needed to identify the CQA, while still maintaining an acceptable product risk profile. To conduct the study, immediate-release ciprofloxacin tablets manufactured via roller compaction were used as a prototype system. Granules were manufactured using an Alexanderwerk WP120 roller compactor and tablets were compressed on a Stokes B2 tablet press. In the early stages of development, prior knowledge was systematically incorporated into the risk assessment using failure mode and effect analysis (FMEA). The factors identified using FMEA were then followed by a quantitative assessed using a Plackett–Burman screening design. Results show that by using prior experience, literature data, and preformulation data the number of experiments could be reduced to an acceptable level, and the use of FMEA and screening designs such as the Plackett Burman can rationally guide the process of reducing the number experiments to a manageable level.KEY WORDS: failure mode effect analysis (FMEA), Plackett–Burman, quality by design (QbD), quality risk management, roller compaction, tablet and ciprofloxacin     

Real-time process/quality control for HPC processing

BACKGROUND: JACIE Standards (FACT Standards in the USA) have been implemented in Europe since 1999. An on-site accreditation inspection took place at our center in January 2004. The purpose of this work was to develop a real-time process/quality control system meeting the JACIE Standards for HPC release. METHODS: Data from 194 HPC processing procedures for autologous transplantation performed over a 5-year period were analyzed. The results of different processing methods applied at our facility were compared: (1) cryopreservation without washing cells (n=50), (2) washing cells (n=87), (3) cell-density separation (n=12) and (4) positive CD34 selection (n=45). RESULTS: Four critical control points were set for the validation of HPC processing: (a) number of lost CD34(+) cells during processing, (b) contamination, (c) viability of the cells after thawing and (d) ability to reconstitute hematopoiesis after transplantation. On the basis of statistical analysis, ranges of acceptable values were defined for each critical control point and for each processing method. Those acceptable values were used for cell release and real-time quality control. DISCUSSION: This study describes a model for the validation of HPC processing and for a real-time process/quality control system for HPC release. Optimization of processing techniques, standardization of methods and comparison between facilities will open the way towards external quality controls and quality improvement.     

Optimal umbilical cord blood collection,processing and cryopreservation methods for sustained public cord blood banking

Background aimsUmbilical cord blood is an established source of stem cells in patients with hematologic malignancies who do not have HLA-compatible matched related or unrelated donors. The success of an umbilical cord blood transplant depends on the dose of total nucleated and CD34+ cells infused. Therefore, collecting, banking and listing high-quality cord blood units with high total nucleated and CD34+ cell dose are essential.MethodsHere the authors describe their cord blood bank's novel collection technique, which involves both in utero and ex utero collection of a single cord blood unit. The authors also evaluated maternal, neonatal and collection parameters that may impact the cell dose.ResultsMaternal gestational age and race, and neonatal weight and sex correlated with the total nucleated cell dose.ConclusionsThe optimized collection of umbilical cord blood is critical for its use as a source of stem cells for transplantation.     

基于FMEA法的剖宫产风险识别与对策研究

目的 帮助医院明确剖宫产手术中的高风险环节及关键流程,切实做好产科安全管理。方法　通过FMEA法与文献研究、头脑风暴、问卷调查及专家咨询相结合的方式,对剖宫产诊疗流程中的风险进行识别。结果　共识别出剖宫产诊疗流程中10项高风险环节,即产后出血、知情同意效果不佳、会诊不及时、羊水栓塞、切口感染、尿路感染、会诊诊断及治疗错误、术前宣教效果不佳、麻醉失误、检查结果有误。结论 FMEA法是一项有效的医疗风险识别工具,能够前瞻性的检测出剖宫产高风险环节.并有针对性地实施干预。     

Environmental risk assessment of dams at constructional phase using VIKOR and EFMEA methods (Case study: Balarood Dam,Iran)

Abstract

The purpose of this study was to assess the environmental risk of Balarood Dam in Iran at constructional phase. The scientific methods used in this research were the Environmental Failure Mode and Effects Analysis (EFMEA) and VIKOR. In the process of environmental risk assessment, the EFMEA method was used first to calculate the risk priority number (RPN) for each environmental aspect. The identified risks were ranked based on RPN values in the next stage. Comparison of the RPN values showed that the risk of pollution of Balarood River, with a RPN of 125, is in the first priority. In addition, the environmental risks, identified during the follow-up phase, were weighted by entropy method based on severity, occurrence probability, and extent of pollution.Then, the VIKOR method, as one of the multicriteria decision-making (MCDM) methods, was run to evaluate and prioritize the potential environmental risks. The risk of water pollution under high, medium and low conditions, with a weight of 1,300, 1,000 and 700, was identified as the most important risk of dam construction. Accordingly, the most important corrective action, proposed to mitigate the high priority environmental risks, is to prevent the discharge of sanitary and industrial wastewater into the river.     

Accommodating clinical trials and other externally manufactured cellular therapy products: challenges,lessons learned and creative solutions

Background aimsThe Division of Transfusion Medicine and Cellular Therapy at New York-Presbyterian/Columbia University Irving Medical Center (NYPH-CUIMC) comprises the immunohematology laboratory and blood bank (transfusion service), hemotherapy/apheresis and the cellular therapy laboratory (CTL). The CTL processes and stores hematopoietic progenitor cells for bone marrow transplantation from all currently acceptable sources, including bone marrow, peripheral blood and umbilical cord blood. The laboratory provides services for the pediatric and adult blood and marrow transplant programs at both NYPH-CUIMC and the Morgan Stanley Children's Hospital of New York-Presbyterian. The laboratory processes and stores approximately 200 cellular therapy products per year, and the division participates in numerous clinical trials within the institution and with external pharmaceutical manufacturing facilities. As a licensed tissue bank, commercial chimeric antigen receptor T-cell products and other cellular-based therapies that are approved by the US Food and Drug Administration (FDA) are routed through the CTL for storage, processing, coordination of transportation, chain of custody and, eventually, thaw and distribution. Currently, we are distributing four such products from Kite Pharma, Novartis and Bristol Meyers Squid. In comparison to the amount of work, we employ a small staff of only four full-time clinical laboratory technologists, one technical specialist, one quality and operations manager and one medical director. In recent years, the growing use of the hematology/oncology service and the introduction of new immunotherapies have put significant pressure on our division to accommodate and scale up operations. Accompanying this growth is a mounting administrative burden and upsurge in regulatory and protocol-specific oversight. The purpose of this article is to share lessons learned and creative solutions to help better accommodate the surge in development of novel cellular therapies.MethodsTo handle this increase in demand, the CTL worked to standardize administrative procedures, implement comprehensive document control solutions, digitize data collection and implement lean design concepts to increase effectiveness and mitigate risk.ResultsDistribution of a standard operating procedure for clinical trial management improved the “on-boarding” process and allowed the laboratory to have more influence in the decision-making process. Implementation of digital workflows and a comprehensive document control system allowed for improved organization of critical documents and proved to be flexible enough to accommodate various protocol-specific requirements. Introduction of visual ques and reorganization of the workspace facilitated better organization, mitigated risk and assisted the laboratory in maintaining regulatory compliance.ConclusionsBetter-defined, structured and controlled laboratory processes helped laboratory management implement new clinical trials and track critical data. Implementing digital solutions using widely available tools like Microsoft SharePoint has proven to be a very secure, low-cost and flexible solution to keeping us “up-to-date” and inspection-ready.     

Quality risk management of the chimeric antigen receptor T cell pharmaceutical circuit in one of the first qualified European centers

Background aimsAccording to European Directive 2001/83/EC, chimeric antigen receptor T (CAR T) cells belong to a new class of medicines referred to as advanced therapy medicinal products (ATMPs). The specific features and complexity of these products require a total reorganization of the hospital circuit, from cell collection from the patient to administration of the final medicinal product. In France, at the cell stage, products are under the responsibility of a cell therapy unit (CTU) that controls, manipulates (if necessary) and ships cells to the manufacturing site. However, the final product is a medicinal product, and as with any other medicine, ATMPs have to be received, stored and further reconstituted for final distribution under the responsibility of the hospital pharmacy. The aim of our work was to perform a risk analysis of this circuit according to International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Q9 guidelines on quality risk management.MethodsWe evaluated the activities carried out by the Saint-Louis Hospital CTU and pharmacy. Process mapping was established to trace all the steps of the circuit and to identify potential risks or failures. The risk analysis was performed according to failure mode, effects and criticality analysis. The criticality of each risk (minor [Mi], moderate [Mo], significant [S] or major [Ma]) was scored, and corrective actions or preventive actions (CAPAs) for Mo, S and Ma risks were proposed.ResultsWe identified five Mo, six S and no Ma risks for the CTU part of the process. The most frequent risk was traceability failure. To reduce its frequency, we developed and validated software dedicated to ATMP activities. Another S risk was non-compliance of CAR T cell-specific steps due to the significant variability between companies. Our CAPA process was to implement procedures and design information sheets specific to each CAR T-cell program. In addition, critical steps were added to the ATMP software. Our CAPA process allowed us to reduce the criticality of identified risks to one Mi, seven Mo and three S. For the pharmacy part of the process, five Mo, two S and one Ma risk were identified. The most critical risk was compromised integrity of the CAR T-cell bag at the time of thawing. In case of unavailability of a backup bag, we designed and validated a degraded mode of operation allowing product recovery. In this exceptional circumstance, an agreement has to be signed between the physician, pharmacy, CTU and sponsor or marketing authorization holder. The implemented CAPA process allowed us to reduce the criticality of risks to three Mi and five Mo.ConclusionsOur risk analysis identified several Mo and S risks but only one Ma risk. The implementation of the CAPA process allowed for controlling some risks by decreasing their frequency and/or criticality or by increasing their detectability. The close collaboration between the CTU and pharmacy allows complete traceability of the CAR T-cell circuit, which is essential to guarantee safe use.     

Considerations for immune effector cell therapy collections: a white paper from the American Society for Apheresis

Background aimsThis white paper was developed to provide leukapheresis guidance for the collection of mononuclear cells from adult and pediatric patients who are destined for immune effector cell (IEC) therapies for commercial and research applications. Currently, there is considerable variability in leukapheresis processes and limited published information regarding best practices relevant to new cellular therapies, especially IECs. Herein the authors address critical leukapheresis questions in five domains to help guide consistent collection processes and ensure high-quality products. The first four domains are onboarding, pre-collection, collection and post-collection, with protocol feasibility, preparation, care and follow-up of the patient/donor at each step, respectively, and technical considerations during collection. The fifth domain of quality assurance focuses on ensuring product potency, purity, safety and auditing.MethodsThe American Society for Apheresis (ASFA) Clinical Applications Committee (IEC Therapy Subcommittee) was charged by the society's board of directors with working collaboratively with other ASFA committees and organizations, including the Foundation for the Accreditation of Cellular Therapy, Association for the Advancement of Blood and Biotherapies, American Society for Transplantation and Cellular Therapy, National Marrow Donor Program and International Society for Cell & Gene Therapy, to develop guidelines regarding leukapheresis collection of cells destined for the manufacture of IEC therapies. After a review of the literature and discussion with members of the involved committees and various institutions, a draft guidance was created and circulated for comment and revision.ResultsCritical aspects of apheresis that could affect the quality and quantity of the leukapheresis product were identified. These areas were then discussed and reviewed. After consensus, the best practice guidelines were proposed and accepted.ConclusionsIn the current era of rapid growth of IEC therapies, it is important to address critical leukapheresis steps to provide high-quality products and more consistent practices and to eliminate redundant efforts.     

Protocol for Development of American Association of Clinical Endocrinology Clinical Practice Guidelines and Consensus Statements: Summary of Methodology,Process, and Policy – 2023 Update

ObjectiveThis 2023 updated protocol summarizes the American Association of Clinical Endocrinology’s (AACE’s) new framework for the development of clinical practice guidelines and other guidance documents that includes changes to methodology, processes, and policies.MethodsAACE has critically reviewed its development processes for guidance documents over the last several years against the National Academy of Medicine Standards for Developing Trustworthy Clinical Practice Guidelines and the Council of Medical Specialty Societies Principles for Development of Specialty Society Clinical Guidelines to determine areas for improvement.ResultsThe new AACE framework for development of guidance documents incorporates many changes, including a revised conflicts of interest (COI) policy; strengthened commitment to collection of disclosures and management of relevant COI during development; open calls to membership for authors; new requirements for authors; new diversity, equity, and inclusion (DEI) policy; new empanelment process that incorporates consideration of DEI; and adoption of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to increase the quality of evidence assessment and standardize recommendation grades and statements, among other improvements.ConclusionsAACE has revised its policies and adopted a completely new methodology for guideline development in support of the mission to elevate the practice of clinical endocrinology to improve patient care. With the use of an evidence-based medicine framework and by continually assessing and improving its processes for development of guidance, AACE strives to deliver trustworthy, unbiased, and up-to-date information that ensures clinician and patient confidence in AACE content. Further, AACE hopes that these enhancements foster a more collaborative approach to development and increase engagement with the worldwide medical community to improve global health.     

Environmental,health, and safety risks of the power lines nearby the human settlements

Advances in technology have not always been in favor of human beings and can lead to the emergence of “emerging contaminants” in human dwellings. These contaminants have taken a new form that is colorless, tasteless, and odorless and invisibly pollute the environment. Due to being intangible, their control and measurement are more difficult than the other types of pollutants. This study is an attempt to identify and assess the risks induced by high-voltage power lines crossing a residential area in southern Iran. To this end, the process of power transmission and the equipment used was initially identified. Afterward, the failure modes of the equipment resulting in the occurrence of risk were detected. In order to measure the strength of the magnetic field, the 3D EMF TESTER was used. The identified risks were scored based on the Environmental failure mode and effects analysis (EFMEA) parameters and a risk priority number (RPN) was assigned to each risk. In the final step, SPSS version 16 software was applied to calculate the risk level and identify the top priority risks. The highest RPN values obtained were related to the health risks so that all identified risks in this group were subjected to an emergency situation. The highest RPN was 360 assigned to “cable (no privacy)” and “power transmission line (non-compliance with privacy standards)”, while the lowest RPN was 60 subjected to disconnect switch (disconnector). Since majority of the identified risks has a high RPN, some mitigating measures were proposed to reduce the risk intensities as much as possible.     

Coronavirus disease 2019 pandemic and allogeneic hematopoietic stem cell transplantation: a single center reappraisal

Background: The coronavirus disease 2019 (COVID-19) pandemic has deeply modified the complex logistical process underlying allogeneic hematopoietic stem cell transplant practices. Aim: In light of these changes, the authors compared data relative to allogeneic transplants carried out from 2018 at their center before (n = 167) and during the pandemic (n = 45). Methods: The authors examined patient characteristics, donor and graft types, cell doses and main transplant outcomes. Moreover, the authors evaluated the rise of costs attributable to additional COVID-19-related procedures as well as the risk of adverse events these procedures conveyed to grafts or recipients. Results: Overall, the number of transplants did not decrease during the pandemic, whereas patients at high relapse risk were prioritized. Transplants were mainly from matched unrelated donors, with a significant decrease in haploidentical related donors. Moreover, the use of bone marrow as a graft for haploidentical transplant was almost abandoned. Cryopreservation was introduced for all related and unrelated apheresis products, with a median storage time of 20 days. Notably, transplant outcomes (engraftment, acute graft-versus-host disease and non-relapse mortality) with cryopreserved products were comparable to those with fresh products. Conclusions: Considering that the emergency situation may persist for months, cryopreserving allogeneic grafts can offer a lifesaving opportunity for patients whose allogeneic transplant cannot be postponed until after the end of the COVID-19 pandemic.     

Multicenter cell processing for cardiovascular regenerative medicine applications: the Cardiovascular Cell Therapy Research Network (CCTRN) experience

Background aimsMulticenter cellular therapy clinical trials require the establishment and implementation of standardized cell-processing protocols and associated quality control (QC) mechanisms. The aims here were to develop such an infrastructure in support of the Cardiovascular Cell Therapy Research Network (CCTRN) and to report on the results of processing for the first 60 patients.MethodsStandardized cell preparations, consisting of autologous bone marrow (BM) mononuclear cells, prepared using a Sepax device, were manufactured at each of the five processing facilities that supported the clinical treatment centers. Processing staff underwent centralized training that included proficiency evaluation. Quality was subsequently monitored by a central QC program that included product evaluation by the CCTRN biorepositories.ResultsData from the first 60 procedures demonstrated that uniform products, that met all release criteria, could be manufactured at all five sites within 7 h of receipt of BM. Uniformity was facilitated by use of automated systems (the Sepax for processing and the Endosafe device for endotoxin testing), standardized procedures and centralized QC.ConclusionsComplex multicenter cell therapy and regenerative medicine protocols can, where necessary, successfully utilize local processing facilities once an effective infrastructure is in place to provide training and QC.     

RPN2与肝癌患者预后及对肝癌细胞生长的作用

目的:探讨核糖蛋白2(ribophorin II,RPN2)在肝细胞肝癌(HCC)组织中的表达和对HCC患者生存的影响,同时分析RPN2对肝癌HepG2细胞生长和克隆形成的作用。方法:应用免疫组化方法和HCC公共芯片数据,从蛋白和m RNA水平检测HCC组织中RPN2的表达,同时分析RPN2与HCC患者临床参数的关系及预后相关性;进一步利用MTS法和克隆形成实验在肝癌HepG2细胞中检测RPN2对细胞生长的作用。结果:98例肝癌组织中,RPN2阳性表达率88.78%,对应癌旁肝组织中,RPN2阳性表达率74.49%;癌组织中RPN2染色评分为5.80±3.15,癌旁肝组织RPN2染色评分为2.13±1.59,肝癌组织中RPN2表达显著上调(P0.001)。3个肝癌公共芯片数据(共522例肝癌)中RPN2的m RNA表达水平同样显著升高(均P0.001)。98例肝癌患者RPN2表达水平与肿瘤直径(P=0.004)、门脉侵袭(P=0.012)和TNM分期(P=0.009)相关;RPN2高表达的患者总体生存期(OS)和无复发生存期(RFS)较RPN2低表达的患者短(OS:P=0.027;RFS:P=0.036)。肝癌HepG2细胞转染RPN2小干扰RNA后,细胞生长能力显著受抑制。结论:RPN2在肝癌中表达显著升高,RPN2的表达与肝癌的恶性进展有关,RPN2显著促进肝癌细胞生长。     

Use FMEA method for environmental risk assessment in ore complex on wildlife habitats

Human activities are the most effective cause of wildlife habitat destruction and loss of quality. Some of these activities are the construction, operation, and utilization of mines. The present study investigates factory activity in the GolGoharSirjanOre Complex (Kerman province) and environmental risk assessment of the activities done by this complex on wildlife habitat. In order to identify the significant aspects of the complex, the Failure Mode and Effects Analysis (FMEA) method is used. To determine the risk priority number, the significant aspects resulted from the multiplication of the criteria including probability of occurrence, the probability of detection, and severity of the effect. Based on the results of the current study, most of the activities of GolGoharSirjan Complex can have a significant adverse impact on the habitat of birds such as bustard Chlamydotisundulata (Vulnerable [VU]) and Podocespleskei, and mammals such as Striped Hyaena (Hyaenahyaena) (Near Threatened [NT]) and Capra aegagrus (Wild Goat) (VU). Some of the most important activities related to the activity include: Crusher (Risk Priority Number [RPN] = 720), the concentration of iron ore (RPN = 640), mining (RPN = 486), Stalker and Reclaiming (RPN = 504), and the transport of heavy machinery (RPN = 432). Significant aspects such as the emission of dust into the air; Nitrogen Oxide (NOX), Sulphur Oxide (SOX), and Hydrogen Sulfide (H2S) gas emissions to air; vibration; noise; and industrial waste discharges significantly influence the environment. The results of measurements of environmental pollutants that are carried out by reliable environmental laboratories have shown that the amount of pollutants mentioned are above the standard limit determined by the Iranian Department of Environment.     

Quality-by-Design II: Application of Quantitative Risk Analysis to the Formulation of Ciprofloxacin Tablets

Qualitative risk assessment methods are often used as the first step to determining design space boundaries; however, quantitative assessments of risk with respect to the design space, i.e., calculating the probability of failure for a given severity, are needed to fully characterize design space boundaries. Quantitative risk assessment methods in design and operational spaces are a significant aid to evaluating proposed design space boundaries. The goal of this paper is to demonstrate a relatively simple strategy for design space definition using a simplified Bayesian Monte Carlo simulation. This paper builds on a previous paper that used failure mode and effects analysis (FMEA) qualitative risk assessment and Plackett-Burman design of experiments to identity the critical quality attributes. The results show that the sequential use of qualitative and quantitative risk assessments can focus the design of experiments on a reduced set of critical material and process parameters that determine a robust design space under conditions of limited laboratory experimentation. This approach provides a strategy by which the degree of risk associated with each known parameter can be calculated and allocates resources in a manner that manages risk to an acceptable level.