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高效液相色谱-二级管阵列检测器法测定美白类、祛斑类化妆品和香波中氢醌、苯酚含量

摘要
样品用甲醇超声提取１ｉ，５ｍｎ离心、滤，ＡｉｎＯＢＸＥｌｓＤ过以ｇｅｔＲＡｃｉｅＸＢ—ＣｌＺｐＮ分析柱分离分析，二级管
阵列检测器检测，外标法定量。氢醌、苯酚分别在７９０— ９９０ｍｇＬ９６６—９．６ｑ／．２７．２／、．９６９０ｎＬ浓度范围内线性关系Ｉｇ
１实验部分
１１主要仪器与试剂．
高效液相色谱仪：ｇｅｔ２０型，Ａｉｎ１０ｌ附带ＤＤ二Ａ极管阵列检测器，国安捷伦公司；美
超声波清洗器：７２４型，国ＥｍＤ一８２德ｌａ公司；高速离心机：３Ｋ型，国Ｓｇａ司；３— ０德ｉｍ公分析天平：Ｌ０Ａ２４型，特勒一托利多仪器（梅上海）限公司；有
测检验祛斑美白类化妆品的质量，证消费者用到保
分别精密称取氢醌、苯酚标准品００９０１１．９、．２２ｇ用甲醇溶解后定容至１０ｍ，０Ｌ棕色容量瓶中，分别
得到０９０、．１ｇｍ．９１２２ｍ／Ｌ的氢醌、酚标准储备苯液，４Ｃ暗处保存。临用时将标准储备液用甲醇于￣稀释成所需浓度的混合标准工作溶液。
２２提取溶剂．
利用氢醌和苯酚标准储备液配制成氢醌浓度依
次为７９０１．４、１６０３．０、９２０ｍｇＬ．２、５８０３．８、９６０７．０／，苯酚浓度依次为９６６１．９、８７４４．８、．９、９３２３．８、８４０

DMEM-F12培养基成分

DMEM/F12培养基说明书产品代号：MD207-050【组成成分】成分 mg/L 成分 mg/L 成分 mg/L无水氯化钙 116.6 L-亮氨酸 59.05 亚油酸 0.042五水硫酸铜 0.0013 L-赖氨酸盐酸盐 91.25 硫辛酸 0.105九水硝酸铁 0.05 L-蛋氨酸 17.24 酚红 8.1七水硫酸亚铁 0.417 L-苯丙氨酸 35.48 1,4-丁二胺二盐酸盐0.081氯化钾 311.8 L-丝氨酸 26.25 丙酮酸钠 55氯化镁 28.64 L-苏氨酸 53.45 维生素H 0.0035无水硫酸镁 48.84 L-丙氨酸 4.45 D-泛酸钙 2.24氯化钠 6999.5 L-天门冬酰胺 7.5 氯化胆碱 8.98无水磷酸二氢钠 54.35 L-天门冬氨酸 6.65 叶酸 2.65磷酸氢二钠 71.02 L-半胱氨酸盐酸盐 17.56 i-肌醇 12.6七水硫酸锌 0.432 L-谷氨酸 7.35 烟酰胺 2.02L-精氨酸盐酸盐 147.5 L-脯氨酸 17.25 盐酸吡哆醛 2L-胱氨酸盐酸盐 31.29 L-色氨酸 9.02 盐酸吡哆醇 0.031L-谷氨酰胺 365 L-酪氨酸 38.4 核黄素 0.219甘氨酸 18.75 L-缬氨酸 52.85 盐酸硫胺 2.17L-组氨酸盐酸盐 31.48 D-葡萄糖 3151 胸苷 0.365 L-异亮氨酸 54.47 次黄嘌呤 2 维生素B12 0.68 【产品指标】外观粉红色固体粉末溶解性完全溶解，溶液澄明。

pH值①加NaHCO3 6.60～7.20②不加NaHCO3 5.50～6.10水分（%）≤5.0渗透压（mOsm/kgH2O）①加NaHCO3 274～302②不加NaHCO3 238～263细菌内毒素（EU/ml）≤10微生物检查（CFU/g）≤1000细胞生长试验细胞形态与标准细胞形态相似细胞数量加10％小牛血清培养4天，细胞密度从104细胞/ml 增加到105细胞/ml。

医疗器械加速老化实验方案及报告

医疗器械加速老化实验方案及报告Title: Experimental Plan and Report for Accelerating Agingof Medical DevicesIntroduction:Experimental Plan:1. Selection of Medical Device:2. Identification of Aging Parameters:Identify the primary aging parameters that can simulatereal-world conditions and affect the device's functionality,such as temperature, humidity, vibration, and mechanical stress. Consult relevant standards and guidelines to determineapplicable parameters for the selected medical device.3. Aging Chamber Setup:Create an aging chamber that replicates the desired aging parameters. Ensure precise control and monitoring of temperature, humidity, and other relevant factors. Calibrate all instruments used for measurements.4. Accelerated Aging Protocol:Develop a protocol that specifies the duration and magnitude of exposure to aging parameters. Consider the expected lifespanof the device, usage conditions, and regulatory requirements.For example, if the device is expected to last for five years,aim to replicate this duration within a shorter period by increasing the intensity of aging parameters.5. Test Execution:Place the medical device inside the aging chamber and expose it to the predetermined aging parameters according to the accelerated aging protocol. Continuously monitor and record any changes in the device's performance, functionality, and safety features. Regularly inspect the device for visible signs of aging, such as discoloration, cracks, or wear.6. Data Collection and Analysis:7. Interpretation of Results:Report:I. Introduction:- Background information on the importance of accelerated aging testing for medical devices.- Brief description of the selected medical device and its relevance.II. Methodology:- Detailed description of the aging parameters used.- Outline of the aging chamber setup, including instruments and calibration procedures.- Explanation of the accelerated aging protocol.III. Results:- Presentation of data collected during the aging process, including measurements, observations, and abnormal behavior.IV. Analysis and Interpretation:- Discussion and interpretation of the results obtained.- Assessment of the impact of aging on the device's functionality and safety.- Identification of any potential design or material improvements.- Suggestions for improvements in the device's design, materials, or manufacturing process.- Highlighting any potential risks or limitations observed during the accelerated aging process.VI. Conclusion:- Summary of the findings obtained from the accelerated aging experiment.- Importance of conducting similar tests for ensuring the safety and efficacy of medical devices.VII. References:- List of all references and sources consulted during the experimental plan and report preparation.。

医疗器械管理-医疗产品可靠性试验-加速实验

医疗产品可靠性试验-加速实验1、加速试验概念加速试验是指在保证不改变产品失效机理的前提下，通过强化试验条件，使受试产品加速失效，以便在较短时间内获得必要信息，来评估产品在正常条件下的可靠性或寿命指标。

通过加速试验，可迅速查明产品的失效原因，快速评定产品的可靠性指标。

2、加速试验的目的与特点进行加速试验的目的可概括如下：（1）为了适应日益激烈的竞争环境；（2）在尽可能短的时间内将产品投入市场；（3）满足用户预期的需要。

加速试验是一种在给定的试验时间内获得比在正常条件下（可能获得的信息）更多的信息的方法。

它是通过采用比设备在正常使用中所经受的环境更为严酷的试验环境来实现这一点的。

由于使用更高的应力，在进行加速试验时必须注意不能引入在正常使用中不会发生的故障模式。

在加速试验中要单独或者综合使用加速因子，主要包括：更高频率的功率循环；更高的振动水平；高湿度；更严酷的温度循环；更高的温度。

3、加速试验分类加速试验主要分为两类，每一类都有明确的目的：（1）加速寿命试验--估计寿命；（2）加速应力试验--确定（或证实）和纠正薄弱环节。

这两类加速试验之间的区别尽管细微，但却很重要，它们的区别主要表现在下述几个方面：作为试验的基础的基本假设、构建试验时所用的模型、所用的试验设备和场所、试验的实施方法、分析和解释试验数据的方法。

表1 对这两类主要的加速试验进行了比较。

4、加速试验的产品层次要明确进行加速试验的产品层次（级别）是设备级还是零部件级，这一点很重要。

某些加速方法只适用于零件级的试验，而有的方法只能用于较高级别的总成（设备），只有少数方法同时适用于零件级和总成（设备）级。

对零件级非常合适的基本假设和建模方法在对较高级别的设备进行试验时可能完全不成立，反之亦然。

表2 列出了在两个主要的级别（设备级和零部件级）上进行试验的信息。

5、先进的加速试验过去，大多数加速试验都是使用单一应力和在定应力谱进行的。

包括周期固定的周期性应力（如温度在规定的上下限之间循环，温度的上限和下限以及温度的变化率是恒定的）。

十二烷基硫酸钠毛细管凝胶电泳法(CE-SDS法)标准操作规程SOP

颁发部门：质量保证部分发部门：分析研究部拷贝号：NO. /目录1目的 (4)2范围 (4)3定义 (4)4环境、健康和安全 (4)5培训 (4)6职责 (4)7程序（内容） (4)7.1原理 (4)7.2实验材料 (4)7.3操作步骤 (5)7.4结果分析 (9)7.5判定标准 (9)7.6注意事项 (9)8相关文件 (10)9参考文献 (10)10流程图 (10)11附录 (10)十二烷基硫酸钠毛细管凝胶电泳法（CE-SDS法）测定记录 (1)十二烷基硫酸钠毛细管凝胶电泳法（CE-SDS法）测定记录(适用于多个样品) (1)1目的规范十二烷基硫酸钠毛细管凝胶电泳法（CE-SDS法）检验的操作过程。

2范围本规程适用于常规十二烷基硫酸钠毛细管凝胶电泳检验，涉及到蛋白质纯度相关指标的测定。

3定义3.1CE-SDS：十二烷基硫酸钠毛细管凝胶电泳。

4环境、健康和安全还原电泳中使用的巯基乙醇为挥发性液体，具有较强烈的刺激性气味，会刺激眼睛、呼吸系统和皮肤，吞食有害，与皮肤接触有毒，取液时穿戴适当的防护服、手套和护目镜或面具。

如不慎与眼睛接触后，请立即用大量清水冲洗并征求医生意见。

该液体对水体环境能产生长期污染等不良影响，切勿倒入下水道，应倒入废液桶，由专业部门回收。

与空气混合、受热、明火可爆，如其燃烧可用二氧化碳、干粉类灭火剂。

储存库房应通风低温干燥，与氧化剂、食品分开储运。

5培训5.1培训部门：分析研究部。

5.2培训对象：分析研究部相关人员。

5.3培训方式和时数：自学，0.5小时。

5.4考核方式：问答。

6职责6.1质量保证部：负责监督本文件的执行。

6.2分析研究部：负责严格执行本规程规定。

7程序（内容）7.1原理该方法是指以弹性石英毛细管为分离管道，以高压直流电场为驱动力，通过目标蛋白在含有胶的溶液中的迁移速率不同而得到分离，较小分子量的分子迁移速度更快则其迁移时间短，较大分子的迁移速度慢则其迁移时间更长。

MEDDEV 2.12-1 REV2_12_1-rev_6-12-2009_en

EUROPEAN COMMISSIONDG ENTERPRISE AND INDUSTRYDirectorate F-Consumer GoodUnit F3- Cosmetic and Medical DevicesMEDICAL DEVICES: Guidance documentMEDDEV 2.12-1 rev 6December 2009GUIDELINESON A MEDICAL DEVICES VIGILANCE SYSTEMThe present guidelines are part of a set of guidelines relating to questions of application of EC-Directives on MEDICAL DEVICEs. They are legally not binding. The guidelines have been carefully drafted through a process of intensive consultation of the various interested parties (competent authorities, Commission services, industries, other interested parties) during which intermediate drafts were circulated and comments were taken up in the document. Therefore, this document reflects positions taken by representatives of interested parties in the MEDICAL DEVICEs sector.Revision 6 of MEDDEV 2.12-1 incorporates technical modifications to Annex 3 (Report Form - Manufacturer's Incident Report). The April 2007 version of MEDDEV 2.12-1 remains otherwise unchanged. The revised Annex 3 will be applicable as of 20 March 2010.T ABLE OF C ONTENTST ABLE OF C ONTENTS (2)1FOREWORD (4)2INTRODUCTION (4)3SCOPE (5)3.1GENERAL PRINCIPLES (6)3.1.1FOR MANUFACTURERS (6)3.1.2FOR MANUFACTURERS OF IVDS (7)3.1.3FOR NATIONAL COMPETENT AUTHORITIES (7)3.1.4FOR USERS (8)4DEFINITIONS (8)4.1ABNORMAL USE (8)4.2AUTHORISED REPRESENTATIVE (8)4.3CORRECTIVE ACTION (8)4.4DRUG / DEVICE COMBINATION PRODUCT (9)4.5EUDAMED (9)4.6FIELD SAFETY CORRECTIVE ACTION (FSCA) (9)4.7FIELD SAFETY NOTICE (FSN) (10)4.8HARM (10)4.9IMMEDIATELY (10)4.10INCIDENT (10)4.11INDIRECT HARM (10)4.12INTENDED PURPOSE (11)4.13MANUFACTURER (11)4.14MEDICAL DEVICE (11)4.15OPERATOR (11)4.16PERIODIC SUMMARY REPORTING (11)4.17SERIOUS PUBLIC HEALTH THREAT (12)4.18TREND REPORTING (12)4.19UNANTICIPATED (12)4.20USE ERROR (12)4.21USER (12)5MANUFACTURERS´ ROLE (12)5.1INCIDENT REPORTING SYSTEM (13)5.1.1CRITERIA FOR INCIDENTs TO BE REPORTED BY MANUFACTURERS TOCOMPETENT AUTHORITIES (13)5.1.2 CONDITIONS FOR PERIODIC SUMMARY REPORTING UNDER THE MEDICALDEVICE VIGILANCE SYSTEM (15)5.1.2.1INCIDENTS DESCRIBED IN A FIELD SAFETY NOTICE (15)5.1.2.2COMMON AND WELL-DOCUMENTED INCIDENTS (15)5.1.3CONDITIONS WHERE REPORTING UNDER THE MEDICAL DEVICE VIGILANCESYSTEM IS NOT USUALLY REQUIRED (16)5.1.3.1DEFICIENCY OF A DEVICE FOUND BY THE USER PRIOR TO ITS USE (16)5.1.3.2EVENT CAUSED BY PATIENT CONDITIONS (16)5.1.3.3SERVICE LIFE OR SHELF-LIFE OF THE MEDICAL DEVICE EXCEEDED (17)5.1.3.4PROTECTION AGAINST A FAULT FUNCTIONED CORRECTLY (17)5.1.3.5 EXPECTED AND FORESEEABLE SIDE EFFECTS (18)5.1.3.6 NEGLIGIBLE LIKELIHOOD OF OCCURRENCE OF DEATH OR SERIOUSDETERIORATION IN STATE OF HEALTH (19)5.1.4TREND REPORTS (19)5.1.5REPORTING OF USE ERROR AND ABNORMAL USE (20)5.1.5.1REPORTABLE USE ERRORS (20)5.1.5.2USE ERROR WHERE REPORTING UNDER THE MEDICAL DEVICE VIGILANCESYSTEM IS NOT USUALLY REQUIRED (20)5.1.5.3CONSIDERATION FOR HANDLING ABNORMAL USE (20)5.1.6DETAILS TO BE INCLUDED IN MANUFACTURER REPORTS (21)5.1.7TIMESCALE FOR THE INITIAL REPORTING OF AN INCIDENT (21)5.1.8TO WHOM TO REPORT (21)5.2HANDLING OF USER REPORTS SUBMITTED TO THE MANUFACTURER BY ANATIONAL COMPETENT AUTHORITY (22)5.3INVESTIGATIONS (22)5.3.1 PRINCIPLES (22)5.3.2ACCESS TO THE DEVICE SUSPECTED TO BE INVOLVED IN THE INCIDENT (22)5.4 OUTCOME OF AN INVESTIGATION AND FOLLOW-UP (23)5.4.1 PRINCIPLES (23)5.4.2FOLLOW-UP REPORT (23)5.4.3FINAL REPORT (23)5.4.4 FIELD SAFETY CORRECTIVE ACTION (23)5.4.4.1NOTIFICATION TO NATIONAL COMPETENT AUTHORITIES (24)5.4.4.2CONTENT OF THE FIELD SAFETY NOTICE (25)6.RESPONSIBILITIES OF NATIONAL COMPETENT AUTHORITY (26)6.1ACTIONS ON A REPORT FROM USERS OR OTHER SYSTEMS (26)6.2RISK EVALUATION AND SUBSEQUENT ACTIONS (27)6.2.1RISK EVALUATION BY THE NATIONAL COMPETENT AUTHORITY (27)6.2.2MONITORING OF MANUFACTURERS SUBSEQUENT ACTIONS (27)6.2.3NATIONAL COMPETENT AUTHORITY ACTIONS (28)6.3CO-ORDINATION BETWEEN COMPETENT AUTHORITIES (28)6.3.1CIRCUMSTANCES WHERE A COORDINATING NATIONAL COMPETENTAUTHORITY IS NEEDED (28)6.3.2DETERMINATION OF THE COORDINATING NATIONAL COMPETENT AUTHORITY296.3.3THE TASKS OF THE CO-ORDINATING NATIONAL COMPETENT AUTHORITY (29)6.3.4SAFEGUARD CLAUSE (30)6.3.5DISSEMINATION OF INFORMATION BETWEEN National COMPETENTAUTHORITIES (30)6.3.6DISSEMINATION OF INFORMATION OUTSIDE NATIONAL COMPETENTAUTHORITIES BY A NATIONAL COMPETENT AUTHORITY (31)6.4COMPLETION OF THE INVESTIGATION (31)7THE ROLE OF THE NOTIFIED BODIES (32)8THE ROLE OF THE COMMISSION (32)9USERS ROLE WITHIN THE VIGILANCE SYSTEM (32)10.1ANNEX 1 EXAMPLES OF INCIDENTs WHICH THE MANUFACTURER SHOULDREPORT (34)10.2ANNEX 2 EXTRACTS FROM DIRECTIVES RELATING TO "MEDICAL DEVICESVIGILANCE" (36)10.3ANNEX 3 REPORT FORM FOR MANUFACTURER’S TO THE NATIONAL COMPETENTAUTHORITY (39)10.4ANNEX 4 EUROPEAN FIELD SAFETY CORRECTIVE ACTION REPORT FORM (44)10.5ANNEX 5 TEMPLATE FOR A FIELD SAFETY NOTICE (48)10.6ANNEX 6 SUGGESTED NATIONAL COMPETENT AUTHORITY REPORT FORMAT (50)10.7ANNEX 7 TITLES OF GLOBAL HARMONISATION TASK FORCE STUDY GROUP 2DOCUMENTS USED IN THE DEVELOPMENT OF THIS MEDDEV AND/OR CITED (53)10.8ANNEX 8 LIST OF THE USED ABBREVIATIONS (54)10.9ANNEX 9 GUIDANCE TO MANUFACTURERS WHEN INVOLVING USERS IN THEVIGILANCE SYSTEM (55)1 FOREWORDThese guidelines on the Medical Device Vigilance System are part of a set of Medical Device Guidelines that promote a common approach by MANUFACTURERs and Notified Bodies involved in the conformity assessment procedures according to the relevant annexes of the directives, and by the National Competent Authorities charged with safeguarding public health.They have been carefully drafted through a process of consultation with various interested parties during which intermediate drafts were circulated and comments were taken up in the documents. Therefore, it reflects positions taken in particular by representatives of National Competent Authorities and Commission Services, Notified Bodies, industry and other interested parties in the MEDICAL DEVICEs sector.The guidelines are regularly updated accordingly with regulatory developments. The latest version of the guidelines should always be used. This revision of these guidelines has: •carefully considered and transposed into the European context the Global Harmonisation Task Force (GHTF)1 international regulatory guidance documents on vigilance and post market surveillance;•addressed the introduction of European medical device database EUDAMED; •amended the document in light of experience with previous clauses.These guidelines are not legally binding. It is recognised that under given circumstances, for example, as a result of scientific developments, an alternative approach may be possible or appropriate to comply with the legal requirements.Nevertheless, due to the participation of the aforementioned interested parties and of experts from National Competent Authorities, it is anticipated that the guidelines will be followed within the Member States and, therefore, work towards uniform application of relevant directive provisions and common practices within Member States.However, only the text of the Directives is authentic in law. On certain issues not addressed in the Directives, national legislation may be different from these guidelines.2 INTRODUCTIONThese guidelines describe the European system for the notification and evaluation of INCIDENTs and FIELD SAFETY CORRECTIVE ACTIONS (FSCA) involving MEDICAL DEVICEs, known as the Medical Device Vigilance System.The principal purpose of the Medical Device Vigilance System is to improve the protection of health and safety of patients, USERs and others by reducing the likelihood of reoccurrence of the INCIDENT elsewhere. This is to be achieved by the evaluation of reported INCIDENTs and, where appropriate, dissemination of information, which could be used to prevent such repetitions, or to alleviate the consequences of such INCIDENTs.These guidelines are intended to facilitate the uniform application and implementation of the Medical Device Vigilance System requirements contained within:1 A list of the used abbreviations is listed in annex 8•the Directive for Active Implantable Medical Devices (AIMD), 90/385/EEC•the Directive for Medical Devices (MDD), 93/42/EEC•the In Vitro Diagnostic Medical Devices Directive (IVDD), 98/79/EC.FIELD SAFETY CORRECTIVE ACTION (FSCA), FIELD SAFETY NOTICE (FSN), USE ERROR and ABNORMAL USE are new concepts introduced in this revision of the guideline to enhance and clarify the European Medical Device Vigilance System while promoting harmonisation with GHTF provisions.The Medical Device Vigilance System is intended to facilitate a direct, early and harmonised implementation of FIELD SAFETY CORRECTIVE ACTION across the Member States where the device is in use, in contrast to action taken on a country by country basis.Corrective action includes, but may not be confined to: a device recall; the issue of a FIELD SAFETY NOTICE; additional surveillance/modification of devices in use; modification to future device design, components or manufacturing process; modification to labelling or instructions for use.3 SCOPEThese guidelines describe the requirements of the Medical Device Vigilance System as it applies to or involves:• MANUFACTURERs2•National Competent Authorities (NCA)•the European Commission•Notified Bodies•USERs and others concerned with the continuing safety of MEDICAL DEVICEsThese guidelines cover the actions to be taken once the MANUFACTURER or National Competent Authority receives information concerning an INCIDENT involving a MEDICAL DEVICE. Information on INCIDENTs which should be reported under the Medical Device Vigilance System may come to the attention of MANUFACTURERs via the systematic procedure to review experience gained from devices in the post-production phase, or by other means (see annexes II, IV, V, VI, VII of MDD and annexes III, IV, VI and VII of IVDD). The term "post-marketing surveillance" as referred to in Annexes 2, 4, 5 in AIMD has the same meaning as the aforementioned "systematic procedure".These guidelines cover Article 8 (AIMD), Article 10 (MDD) and Article 11 (IVDD) outlining the obligations of Member States upon the receipt of INCIDENT reports, from MANUFACTURERs or other sources, concerning any MEDICAL DEVICE. They also include guidance to National Competent Authorities about the issue and receipt of information from National Competent Authorities outside Europe who are involved in the GHTF National Competent Authority Report (NCAR) exchange programme.These guidelines are relevant to INCIDENTs occurring within the Member States of the European Economic Area (EEA) and Switzerland with regard to:•a) devices which carry the CE-mark2 including their Authorised Representatives and persons responsible for placing on the market, see section 4 on definitions.•b) devices that do not carry the CE-mark but fall under the directives scope (e.g. custom made devices)•c) devices that do not carry the CE mark because they were placed on the market before the entry into force of the medical devices directives.•d) devices that do not carry the CE-mark but where such INCIDENTs lead to CORRECTIVE ACTION(s) relevant to the devices mentioned in a), b) and c).These guidelines cover FIELD SAFETY CORRECTIVE ACTION relevant to CE-marked devices which are offered for sale or are in use within the EEA and Switzerland.These guidelines make no recommendations on the structure of the systems by which MANUFACTURERs gather information concerning the use of devices in the post-production phase, of which the Medical Device Vigilance System is an integral part. Such recommendations are outside the scope of this document.3.1 GENERAL PRINCIPLES3.1.1 FOR MANUFACTURERS•The MANUFACTURER or his AUTHORISED REPRESENTATIVE shall notify the relevant National Competent Authority about INCIDENTs and FIELD SAFETY CORRECTIVE ACTIONs when the reporting criteria are met (see section 5.1 and 5.4). •The MANUFACTURER has the responsibility for investigating INCIDENTs and for taking any CORRECTIVE ACTION necessary (see section 5.2 and 5.3).•The MANUFACTURER should ensure that these guidelines are made known to their AUTHORISED REPRESENTATIVEs within the EEA and Switzerland, persons responsible for placing devices on the market and any other agents authorised to act on their behalf for purposes related to medical devices vigilance, so that the MANUFACTURERs' responsibilities may be fulfilled.•The MANUFACTURER should ensure that their AUTHORISED REPRESENTATIVE within the EEA and Switzerland, persons responsible for placing devices on the market and any other agents authorised to act on their behalf for purposes relating to medical devices vigilance, are kept informed of INCIDENT reports as appropriate.•Where an INCIDENT occurs as a consequence of the combined use of two or more separate devices (and/or accessories) made by different MANUFACTURERs, each MANUFACTURER should submit a report to the relevant National Competent Authority (see section 5.1)•MANUFACTURERs must keep the Notified Body advised of issues occurring in the post production phase affecting the certification (see the relevant annexes of the relevant directives and section 7 of this document). This would include relevant changes derived from the vigilance system.The act of reporting an INCIDENT to a National Competent Authority is not to be construed as an admission of liability for the INCIDENT and its consequences. Written reports may carry a disclaimer to this effect.When placing on the market of a particular model of MEDICAL DEVICE ceases, the MANUFACTURER’s vigilance reporting obligations under the Medical Device Directives remain. However, a MANUFACTURERs legal trading arrangements change with mergers and acquisitions etc. Where the vigilance and other post market surveillance obligations are being transferred to another legal entity it is important that post market surveillance activitiescontinue and that Competent Authorities are appraised of the implications and provided with new contact details as soon as possible, so that any detrimental effects on the functioning of the vigilance system are minimised.For a complete description of the MANUFACTURER’s role in the Medical Device Vigilance System, see section 5 of these guidelines.3.1.2 FOR MANUFACTURERS OF IVDSVigilance reporting for IVDs may be more difficult since IVDs do not generally come into contact with patients. Therefore, it can be difficult to demonstrate direct HARM to patients, unless the device itself causes deterioration in state of health. HARM to patients is more likely to be indirect - a result of action taken or not taken on the basis of an incorrect result obtained with an IVD. Whether as a result of direct or INDIRECT HARM, INCIDENTs should be reported.It may be difficult to determine if a serious deterioration in the state of a patient’s health was or could be the consequence of an erroneous result obtained with an IVD, or if the HARM was the consequence of an error by the USER or third party. There should be a predisposition to report under such circumstances (see section 5.1).In the case of potential errors by USERs or third parties, labelling and instructions for use should be carefully reviewed for any possible inadequacy. This is particularly true for devices used for self-testing where a medical decision may be made by the patient. Inadequacies in the information supplied by the MANUFACTURER that led or could have led to HARM to USERs, patients or third parties should be reported.In particular, it can be extremely difficult to judge events in which no HARM was caused, but where HARM could result if the event was to occur again elsewhere.3.1.3 FOR NATIONAL COMPETENT AUTHORITIESFor the purposes of Medical Devices Vigilance System, Member States are represented by appointed National Competent Authorities, their vigilance contact points being listed on the European Commission web site:http://ec.europa.eu/enterprise/medical_devices/contact_links_en.htm•The National Competent Authority monitors the investigation of the INCIDENT carried out by the MANUFACTURER.•The National Competent Authority should take any further action that may be necessary to supplement the actions of the MANUFACTURER.•Depending on the outcome to the investigation, any information necessary for the prevention of further INCIDENTs (or the limitation of their consequences) should be disseminated by the National Competent Authority.•Member States should ensure that organisations and individuals involved in purchasing MEDICAL DEVICEs and in the provision of health-care are aware that their co-operation is vital in providing the first link in the vigilance chain. In order to enhance the efficiency of the Medical Device Vigilance System, National Competent Authorities should encourage the reporting of INCIDENTs by the USER and other professionals involved in the distribution, the delivery or putting in to service of the device. This includes organisations and individuals responsible for providing calibration and maintenance for MEDICAL DEVICEs. Such reports may be made directly to the MANUFACTURER or to the National Competent Authority as well depending on national practice.Information held by National Competent Authorities in connection with the Medical Device Vigilance System is to be held in confidence, as defined by the relevant articles of the directives3. However, any INCIDENT report should be available on request, and in confidence, to the other European Competent Authorities and to other National Competent Authorities participating in the GHTF exchange programme.For a complete description of the National Competent Authority’s role in the Medical Device Vigilance System, see section 6 of this guideline.USERS3.1.4 FOR•USERs should report INCIDENTs with MEDICAL DEVICEs to the MANUFACTURER or to the National Competent Authority depending on national practice.•Once corrective (or other) action is identified, hospital administrators, medical practitioners and other health-care professionals, and USER representatives responsible for the maintenance and the safety of MEDICAL DEVICEs, can take the necessary steps.Such steps should, where practicable, be taken in co-operation with the MANUFACTURER.For a complete description of the USER’s role in the Medical Device Vigilance System, see section 9 of this guideline.4 DEFINITIONS4.1 ABNORMAL USEAct or omission of an act by the OPERATOR or USER of a MEDICAL DEVICE as a result of conduct which is beyond any means of risk control by the MANUFACTURER.Reference: EN IEC 60601-1-64.2 AUTHORISED REPRESENTATIVEAny natural or legal person established in the Community who, explicitly designated by the MANUFACTURER, acts and may be addressed by authorities and bodies in the Community instead of the MANUFACTURER with regard to the latter’s obligations under the directive.4.3 CORRECTIVE ACTIONAction to eliminate the cause of a potential nonconformity or other undesirable situation. NOTE1: There can be more than one cause for non-conformity.NOTE 2: Corrective action is taken to prevent recurrence whereas preventive action is taken to prevent occurrence.Reference: EN ISO 9000:2000, 3.6.53 AIMD 15, MDD 20 and IVDD 204.4 DRUG / DEVICE COMBINATION PRODUCTA MEDICAL DEVICE incorporating a medicinal product or substance where the action of the medicinal product or substance is ancillary to that of the device. In this case, the lead directive are the Medical Devices Directives (AIMD, MDD).4.5 EUDAMEDThe European database for MEDICAL DEVICEs EUDAMED is to centralise:•data relating to registration of MANUFACTURERS and MEDICAL DEVICES placed on the Community market,•data relating to certificates issued, modified, supplemented, suspended,,withdrawn or refused,•data obtained in accordance with the vigilance procedure.Reference: Article 14a of MDD and article 10 of IVDD.4.6 FIELD SAFETY CORRECTIVE ACTION (FSCA)A FIELD SAFETY CORRECTIVE ACTION is an action taken by a MANUFACTURER to reduce a risk of death or serious deterioration in the state of health associated with the use of a MEDICAL DEVICE that is already placed on the market. Such actions should be notified via a FIELD SAFETY NOTICE.NOTE 1:The FSCA may include- the return of a MEDICAL DEVICE to the supplier;- device modification;- device exchange;- device destruction;- retrofit by purchaser of MANUFACTURER's modification or design change;- advice given by MANUFACTURER regarding the use of the device (e.g. where the device is no longer on the market or has been withdrawn but could still possibly be in usee.g. implants or change in analytical sensitivity or specificity for diagnostic devices)A device modification can include:- permanent or temporary changes to the labelling or instructions for use;- software upgrades including those carried out by remote access;- modification to the clinical management of patients to address a risk of death or serious deterioration in state of health related specifically to the characteristics of the device. For example:- For implantable devices it is often clinically unjustifiable to explant the device.Corrective action taking the form of special patient follow-up, irrespective ofwhether any affected un-implanted devices remain available for return, constitutesFSCA.- For any diagnostic device (e.g. IVD, imaging equipment or devices) the recall of patients for retesting or the retest or review of previous results constitutes FSCA.- advice relating to a change in the way the device is used e.g. IVD MANUFACTURER advises revised quality control procedure -use of third party controls or more frequent calibration or modification of control values for IVDs.NOTE 2: This guideline uses the definition of FSCA as synonym for recall mentioned in article 10(1), paragraph 1b) of the MDD and Article 11 IVD Directive since there is no harmonised definition of recall.4.7 FIELD SAFETY NOTICE (FSN)A communication to customers and/or USERs sent out by a MANUFACTURER or its representative in relation to a Field Safety Corrective Action.4.8 HARMPhysical injury or damage to the health of people, or damage to property or the environment. Reference: ISO/IEC Guide 51:19994.9 IMMEDIATELYFor purposes of this guideline, IMMEDIATELY means without any delay that could not be justified.4.10 INCIDENT“Any malfunction or deterioration in the characteristics and/or performance of a device, as well as any inadequacy in the labeling or the instructions for use which, directly or indirectly, might lead to or might have led to the death of a patient, or USER or of other persons or to a serious deterioration in their state of health.”Reference: Article 10 of the MDDNote 1: There is a similar definition in Article 8 of the AIMD and Article 11 IVD Directive with minor wording differences.Note 2: A description of “serious deterioration in the state of health” is given in section 5.1.1.(C) of this document.4.11 INDIRECT HARMSome diagnostic devices and all IVDs do not act directly on the individual. HARM may occur as a consequence of the medical decision, action taken/not taken on the basis of information or result(s) provided by the device.Examples include• misdiagnosis,•delayed diagnosis,• delayed treatment,• inappropriate treatment,•transfusion of inappropriate materials.For self-testing devices, a medical decision may be made by the USER of the device who is also the patient.4.12 INTENDED PURPOSEThe use for which the device is intended according to the data supplied by the MANUFACTURER on the labelling, in the instructions and/or in promotional materials. Reference: Article 1.2 (h) of the IVDD and Article 1.2 (g) of the MDD4.13 MANUFACTURERThe natural or legal person with responsibility for the design, manufacture, packaging and labelling of a device before it is placed on the market under his own name, regardless of whether these operations are carried out by that person himself or on his behalf by a third party.Reference: Article 1.2 (f) of the IVDD and Article 1.2 (f) of the MDD4.14 MEDICAL DEVICEFor the purpose of the Medical Devices Directives 90/385/EEC, 93/42/EEC and 98/79/EEC, any instrument, apparatus, appliance, material or other Article, whether used alone or in combination, including the software necessary for its proper application intended by the MANUFACTURER to be used for human beings for the purpose of:- diagnosis, prevention, monitoring, treatment or alleviation of disease,- diagnosis, monitoring, treatment, alleviation of or compensation for an injury or handicap,- investigation, replacement or modification of the anatomy or of aprocess,physiological-control of conception,and which does not achieve its principal intended action in or on the human body by pharmacological, immunological or metabolic means, but which may be assisted in its function by such means.4.15 OPERATORPerson handling equipment.4.16 PERIODIC SUMMARY REPORTINGPERIODIC SUMMARY REPORTING is an alternative reporting regime that is agreed between the MANUFACTURER and the National Competent Authority for reporting similarINCIDENTs with the same device or device type in a consolidated way where the root cause is known or an FSCA has been implemented.4.17 SERIOUS PUBLIC HEALTH THREATAny event type which results in imminent risk of death, serious deterioration in state of health, or serious illness that requires prompt remedial action.This would include:•events that are of significant and unexpected nature such that they become alarming as a potential public health hazard, e.g. human immunodeficiency virus (HIV) or Creutzfeldt-Jacob Disease (CJD). These concerns may be identified by either the National Competent Authority or the MANUFACTURER.•the possibility of multiple deaths occurring at short intervals.Reference: GHTF SG2 N33R114.18 TREND REPORTINGA reporting type used by the MANUFACTURER when a significant increase in events not normally considered to be INCIDENTs according to section 5.1.3. occurred and for which pre-defined trigger levels are used to determine the threshold for reporting.NOTE: GHTF SG2 document N36 'MANUFACTURER's TREND REPORTING of Adverse INCIDENTs' provides useful guidance (see annex 7).'4.19 UNANTICIPATEDA deterioration in state of health is considered UNANTICIPATED if the condition leading tothe event was not considered in a risk analysis.NOTE: Documented evidence in the design file is needed that such analysis was used to reduce the risk to an acceptable level, or that this risk is well known by the intended USER. 4.20 USE ERRORAct or omission of an act, that has a different result to that intended by the MANUFACTURER or expected by the OPERATOR of the MEDICAL DEVICE.4.21 USERThe health care institution, professional, carer or patient using or maintaining MEDICAL DEVICES.5 MANUFACTURERS´ ROLE5.1 INCIDENT REPORTING SYSTEMThe MANUFACTURER or their AUTHORISED REPRESENTATIVE must submit an initial INCIDENT report to the National Competent Authority for recording and evaluation. Each initial report must lead to a final report unless the initial and the final report are combined into one report. But not every INCIDENT report will lead to a corrective action.As a general principle, there should be a pre-disposition to report rather than not to report in case of doubt on the reportability of an INCIDENT.Reference to the following considerations may be made in the report, or should be kept on file by the MANUFACTURER in the case of a decision not to report.INCIDENTs which occurred outside the EEA and Switzerland and do not lead to a FIELD SAFETY CORRECTIVE ACTION relevant to these geographic areas do not need to be reported. Incidents which occurred outside the EEA and Switzerland and led to a FIELD SAFETY CORRECTIVE ACTION relevant to the above-mentioned geographical areas must be reported as a FIELD SAFETY CORRECTIVE ACTION.Where appropriate, MANUFACTURERs should notify their AUTHORISED REPRESENTATIVE, persons responsible for placing devices on the market and any other agents (e.g. distributors) authorised to act on their behalf of INCIDENTs and FSCA reported under the Medical Device Vigilance System.If the MANUFACTURER is located outside the EEA and Switzerland, a suitable contact point within should be provided. This may be the MANUFACTURER's AUTHORISED REPRESENTATIVE, persons responsible for placing devices on the market or any other agent authorised to act on their behalf for purposes relating to Medical Devices Vigilance.Any report should not be unduly delayed because of incomplete information.5.1.1 CRITERIA FOR INCIDENTs TO BE REPORTED BY MANUFACTURERS TOCOMPETENT AUTHORITIESAny event which meets all three basic reporting criteria A – C listed below is considered as an INCIDENT and must be reported to the relevant National Competent Authority. The criteria are that:A: An event has occurredThis also includes situations where testing performed on the device, examination of the information supplied with the device or any scientific information indicates some factor that could lead or has led to an event.Typical events include, but are not limited to:a) A malfunction or deterioration in the characteristics or performance.A malfunction or deterioration should be understood as a failure of a device to perform in accordance with its INTENDED PURPOSE when used in accordance with the MANUFACTURER’s instructions.。

临床DM公告-总局关于发布药物临床试验数据管理与统计分析的计划和报告指导原则的通告(2016年第113号)

附件药物临床试验数据管理与统计分析的计划和报告指导原则一、前言规范的数据管理计划有助于获得真实、准确、完整和可靠的高质量数据；而详细的统计分析计划则有助于保证统计分析结论正确和令人信服。

为保证临床试验数据的质量和科学评价药物的有效性与安全性，必须事先对数据管理工作和统计学分析原则制定详细的计划书。

在试验完成时，对试验中的数据管理和统计分析工作进行全面完整的总结至关重要，通过数据管理报告真实反映临床试验过程中的数据质量和试验样本特征，通过统计分析报告为临床试验总结报告的内容和研究结论提供主要依据。

因此，在药物上市注册时，监管部门将数据管理计划和报告与统计分析计划和报告视为评价临床试验结果的重要文件和依据。

虽然我国《药物临床试验质量管理规范》（Good Clinical Pr actice，GCP）中对药物临床试验数据管理与统计分析进行了原则要求，且国家食品药品监督管理总局已发布的有关药物临床试验及其统计学的相应技术指南也涉及数据管理和统计分析工作的主要环节，但针对数据管理计划和报告、统计分析计划和报告却没有详细的技术规范和指导性建议。

因此，本技术指导原则对此进行了较为详细的介绍和阐述，并提出具体要求，旨在为临床试验的数据管理和统计分析人员提供技术指导，帮助其更好地完成相关工作以达到监管要求。

二、数据管理的计划和报告（一）一般考虑数据管理计划（Data Management Plan, DMP）是由数据管理人员依据临床试验方案书写的一份动态文件，它详细、全面地规定并记录某一特定临床试验的数据管理任务，包括人员角色、工作内容、操作规范等。

数据管理计划应在试验方案确定之后、第一位受试者筛选之前定稿，经批准后方可执行。

通常数据管理计划需要根据实际操作及时更新与修订。

数据管理工作涉及多个单位或业务部门，包括数据管理、临床研究者、统计分析、医学事务、临床监查、临床稽查等单位或部门。

数据管理的职责可分为负责、参与、审核、批准、告知等，各单位/部门在数据管理各步骤的职责不尽相同。

一种改善全血样本测值的D-二聚体测定试剂盒、制备方法及应用[发明专利]

专利名称：一种改善全血样本测值的D-二聚体测定试剂盒、制备方法及应用
专利类型：发明专利
发明人：刘道锦,赵畅,陈婷,黄爱,伍卫姣,张雪娇,舒芹
申请号：CN202010771207.4
申请日：20200804
公开号：CN111896757A
公开日：
20201106
专利内容由知识产权出版社提供
摘要：本发明提供了一种改善全血样本测值的D‑二聚体测定试剂盒，属于生物检测技术领域，包括试剂1和试剂2，试剂1包括缓冲液、电解质、十八胺聚氧乙烯醚、促凝剂、离散剂和防腐剂；所述试剂2为胶乳试剂。

该试剂盒可有效定量测定全血样本中D‑二聚体含量，并能提高低值样本检测的精密度。

本发明还提供了一种改善全血样本测值的D‑二聚体测定试剂盒的制备方法及应用。

申请人：武汉生之源生物科技股份有限公司
地址：430000 湖北省武汉市东湖开发区高新大道818号高科医疗器械园B11号1楼、2楼、3楼国籍：CN
代理机构：北京众达德权知识产权代理有限公司
代理人：张晓冬
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弗元生物ITS ITS-E细胞培养添加物说明书

1/ 1弗元（上海）生物科技有限公司网址：邮箱：***********************弗元生物ITS/ITS-E细胞培养添加物(100×)说明书产品编号：FY600201-10MLFY600202-10ML存储条件：2-8 ℃避光保存，有效期18个月。

产品简介：本产品不含酚红。

ITS(Insulin-Transferrin-Selenium)细胞培养添加物基本成分为胰岛素、人转铁蛋白和亚硒酸钠，根据实验需要加入乙醇胺。

一定条件下添加能够促进细胞增殖和减少细胞对血清的需求。

常用于配制低血清和无血清培养基，可以添加到RPMI-1640培养基、MEM等培养基中，具体使用时根据需求自行判断。

胰岛素是一种多肽激素，对哺乳动物细胞具有多效合成代谢作用，促进葡萄糖和氨基酸的摄取、脂肪生成、单价阳离子和磷酸盐的转运、蛋白质和核酸的合成。

转铁蛋白是细胞内铁的载体，可能有助于减少氧自由基和过氧化物的毒性水平。

亚硒酸钠是谷胱甘肽过氧化物酶和其他蛋白质的辅助因子，是培养基中的抗氧化成分。

乙醇胺可以作为磷酸甘油酯生物合成的前体，磷酸甘油酯对细胞膜结构和细胞器结构至关重要。

EBSS缓冲液溶解各成分。

适用实验与使用方法：适用实验：ITS适用于RPMI-1640和Earle's等基础培养基的营养添加。

成软骨诱导培养基中常作为添加物，可能用以满足成软骨对硒的需要。

ITS-E适用于F12，DMEM/F12，DMEM, Earle's等基础培养基的添加物。

在一些细胞的诱导分化实验中配合诱导因子使用可提高分化效率和细胞活性。

使用方法（仅作为参考）：1.将ITS/ITS-E细胞培养添加物(100×)按1:100的比例加入到培养基中。

2.在低血清或者无血清培养基中添加该产品。

3.适用于细胞的体外生长或分化。

注意事项：1.本产品仅用于科学研究。

2.2-8℃避光保存，切勿冻存。

高效液相色谱法同时测定粳米中D(-)-抗

高效液相色谱法同时测定粳米中D(-)-抗坏血酸和L(+)-抗坏血酸的方法优化曾雪仪（肇庆市食品检验所，广东肇庆 526000）摘　要：建立了一种利用高效液相色谱高回收率、快速灵敏地检测粳米中D(-)-抗坏血酸和L(+)-抗坏血酸和抗坏血酸总量的方法。

样品中的抗坏血酸以偏磷酸为提取剂，采用冰浴且二次超声的提取方式，以L-半胱氨酸还原脱氢抗坏血酸为还原型抗坏血酸后测定L(+)-抗坏血酸总量。

以0.1%磷酸∶甲醇=98∶2为流动相，用二极管阵列检测器测定。

结果表明，L （+）-抗坏血酸和D（-）-抗坏血酸在0.5～50.0 μg·mL-1线性良好（r=0.999 96），检出限均为0.13 mg/100 g。

以阴性粳米样品采用低、中、高浓度进行3水平加标回收实验，L（+）-抗坏血酸的回收率为96.0%～99.8%，相对标准偏差为0.65%～1.00%；D（-）-抗坏血酸的回收率为98.8%～101.6%，相对标准偏差为0.68%～1.21%。

该方法不仅达到国家标准的要求，而且具有绿色、稳定、高灵敏及高回收率的特点。

关键词：L(+)-抗坏血酸；粳米；D(-)-抗坏血酸；高效液相色谱法Optimization of Simultaneous Determination of D(-)-Ascorbic Acid, L(+)-Ascorbic Acid and Ascorbic Acid in Japonica Rice by High Performance Liquid ChromatographyZENG Xueyi(Zhaoqing Institute of Food Inspection, Zhaoqing 526000, China) Abstract: A rapid and sensitive method for the determination of D(-)-ascorbic acid, L(+)-ascorbic acid and ascorbic acid in japonica rice with high recovery and high performance liquid chromatography was established. The ascorbic acid in the sample was extracted by ice bath and secondary ultrasound, and the total amount of L(+)-ascorbic acid was determined by using L-cysteine to reduce dehydroascorbic acid as reduced ascorbic acid. Using 0.1% phosphoric acid∶methanol=98∶2 as the mobile phase, it was determined by a diode array detector. The results showed that L(+) -ascorbic acid and D(-)-ascorbic acid had good linearity between 0.5～50.0 μg·mL-1 (r=0.999 96), the limits of detection were 0.13 mg/100 g. The recovery of L(+)-ascorbic acid was 96.0%～99.8%, and the relative standard deviation was 0.65%～1.00%. The recoveries of D(-)-ascorbic acid were 98.8%～101.6% with relative standard deviations of 0.68%～1.21%. The method not only meets the requirements of national standards, but also has the characteristics of green, stable, high sensitivity and high recovery rate.Keywords: L(+)-ascorbic acid; japonica rice; D(-)-ascorbic acid; high-performance liquid chromatography抗坏血酸是人体必不可缺的微量营养元素之一，它不仅广泛参加机体的多项生命活动，还有助于增强免疫力、抗衰老、抵御心血管疾病和动脉硬化[1-2]。

DMtest 1.0.0 产品说明说明书

Package‘DMtest’October12,2022Type PackageTitle Differential Methylation Tests(DMtest)Version1.0.0Date2021-07-22Author James Dai[aut,cre],Xiaoyu Wang[aut]Maintainer James Dai<******************>Description Several tests for differential methylation in methylation array data,including one-sided differential mean and variance test.Methods used in the package re-fer to Dai,J,Wang,X,Chen,H and others(2021)``Incorporating increased variability in discov-ering cancer methylation markers'',Biostatistics,submitted.Depends R(>=3.5.0)Imports matrixStats,stats,foreach,parallel,doParallelLicense GPL(>=2)NeedsCompilation noLazyData trueRoxygenNote7.1.1Suggests knitr,markdownVignetteBuilder knitrRepository CRANDate/Publication2021-07-2606:50:06UTCR topics documented:beta (2)covariate (2)dmvc (3)Index512covariate beta Example DNA methylation data for dmvc functionDescriptionDNA methylation data from TCGA-COADUsagedata(beta)FormatAn object of class"matrix"with with500rows and334columns.Each row is a CpG,each column is a sampleExamplesdata(beta)covariate Example covariate data for dmvc functionDescriptionCovariate data for334TCGA-COAD samplesUsagedata(covariate)FormatAn object of class"matrix"with with334rows and3vaiables.group Whether the sample is normal or tumor,normal:0,tumor:1gender Female or Maleage age(31–90)Examplesdata(covariate)dmvc3 dmvc Perform DMC,DVC,DMVC,and DMVC+tests for genome-wideCpGs in methylation arrays.DescriptionThis function implements an algorithm for computing various tests of mean and variance differ-ences,including the DMVC+test that speciﬁcally addresses the hypermethylation and hypervari-ability for cancer-speciﬁc CpGsUsagedmvc(beta=beta,covariate=covariate,npermut=100,permut.seed=100,corenumber=1)Argumentsbeta Methylation beta value matrix,row for CpGs,column for samples.The matrix has sample name as the column names,and CpG names as the row names.covariate covariate matrix,a data frame including all covariates in the regression model, whose row represents for samples,column represents different covariates.Thematrix has sample names as the row names.The matrix must include a"group"column,which is a binary indicator(0for normal and1for tumor)to deﬁne twogroups of samples to be compared.npermut The number of permutations for computing the correlation that is needed for the joint testspermut.seed The random seed used by permutation for joint testscorenumber The number of cores to be used for joint tests;if corenumber>1,a parallel com-puting version will be used to speed up the computationValueA data frame with the following columns.Mean_normal Mean of beta values for normal samples.Mean_tumor Mean of beta values for tumor samples.Mean_all Mean of beta values for all samples.SD_normal Standard deviation of beta values for normal samples.SD_tumor Standard deviation of beta values for tumor samples.SD_all Standard deviation of beta values for all samples.DMCP p-value from DMC test.DVCP p-value from DVC test.Joint1P Joint test for DMVC+(test for hypermethylation and increased variance in can-cer samples).4dmvc Joint2P Joint test for DMVC(test for differential methylation in both direction and in-creased variance in cancer samples).LRT1Likelihood ratio test statistics for joint test1.LRT2Likelihood ratio test statistics for joint test2.pho Correlation value computed by permutations.ReferencesDai,J,Wang,X,Chen,H and others.(2021).Incorporating increased variability in discovering cancer methylation markers,Biostatistics,submitted.Examplesdata(beta)data(covariate)out=dmvc(beta=beta,covariate=covariate)Index∗datasetsbeta,2covariate,2beta,2covariate,2dmvc,35。

trainingchendu

二○二一年三月十八日
30
中红外线技术 — 福斯Filter 技术
丹麦FOSS公司生产产品MilkoScan 系列
名称
发行年份
MilkoScan 300/203 MilkoScan 104 MilkoScan 605 MilkoScan 130 MilkoScan 300 MilkoScan 4000 MilkoScan 50 MilkoScan S50
红外线滤光片技术应用评估
该技术适合用于原料奶的检测，因为原料奶的成份比较稳定，目前已经开发出的滤光片基本可以满足用户按质论价的项目需求，因此该技术被广泛用于原料奶的按质论价体系和 DHI(Dairy Herd Improved,)体系。
Dedicated Analytical Solutions
二○二一年三月十八日
Dedicated Analytical Solutions
链条管理环节三：乳品厂收购（从奶牛到消费者）
Dedicated Analytical Solutions
乳品厂对奶车检查，获得高质量的原料奶 •成分分析 •细菌分析
•掺水，游离脂肪酸分析 •抗生素分析
Quality defects may be traced back to the farmer via the payment samples
1000
1200
二○二一年三月十八日
Pin num ber
28
乳品红外光谱技术进展简述
Dedicated Analytical Solutions
二○二一年三月十八日
29
红外线光谱技术
滤光片技术 Filter
干涉仪技术(FTIR) Interferometer

预测牛乳货架期的时间--温度指示器的研制

预测牛乳货架期的时间--温度指示器的研制谷雪莲;杜巍;华泽钊;刘彦臣【期刊名称】《农业工程学报》【年(卷),期】2005(21)10【摘要】利用生物化学方法实验研究了牛乳品质与存放温度、时间的关系,并根据菌落总数和酸度作为依据得出时间-温度-货架期曲线.应用单片机技术,研制出能实测和记录冷藏链时间-温度变化和剩余货架期的指示器.以期实现冷藏链中牛乳的品质监测.研究结果表明,存放过程中,菌落总数随着温度的升高和时间的延长而增加,新鲜度随温度的升高和时间的延长而降低.对于经历了不同温度-时间存放的牛乳,应用指示器实测的剩余货架期和生物化学实验得到的结果相比,偏差在0.5 d以内.当牛乳剩余货架期少于1 d时,指示器发出声音报警.【总页数】5页(P142-146)【作者】谷雪莲;杜巍;华泽钊;刘彦臣【作者单位】上海理工大学食品与生物技术研究所,上海,200093;上海理工大学食品与生物技术研究所,上海,200093;上海理工大学食品与生物技术研究所,上海,200093;东北电力大学自动化工程学院,吉林,132012【正文语种】中文【中图分类】S879.1;TS252.26【相关文献】1.电子式时间-温度指示器监测牛乳货架期的实验研究 [J], 谷雪莲;刘宝林;华泽钊;王欣;刘彦臣2.酶型时间温度指示器监测冷鲜猪肉贮藏货架期 [J], 乔磊;卢立新※;唐亚丽;刘志刚3.葡萄冷链品质的时间-温度指示器模糊推理预测 [J], 张小栓;孙格格;杨林;郭永洪;马常阳4.扩散型时间-温度指示器在预测奇异果品质中的应用 [J], 杨加敏;胥义5.时间-温度指示器在食品保质期预测中的应用 [J], 刘冬青;陈朴;臧鹏;杜秉健;徐楠;向红因版权原因，仅展示原文概要，查看原文内容请购买。

高效液相色谱法测定血中伊立替康及活性代谢物SN-38浓度

高效液相色谱法测定血中伊立替康及活性代谢物SN-38浓度鞠晓宇;罗雪梅;葛卫红;王友群【期刊名称】《药学与临床研究》【年(卷),期】2015(000)003【摘要】目的：建立高效液相色谱法同时测定结直肠癌患者血中的伊立替康（CPT-11）及其活性代谢物7-乙基-10-羟基喜树碱（SN-38）的浓度，并对我院基因型指导给药方案进行评价。

方法：以2μg·mL-110-羟基喜树碱作为内标，先用100μL 10%高氯酸沉淀蛋白，再用50μL 10%高氯酸酸化血浆。

采用Agilent ZORBAX Eclipse C8色谱柱（4.6 mm×150 mm，5μm）对CPT-11和SN-38进行分离；以0.05 mol·L-1的磷酸二氢钠-乙腈-三乙胺（75∶25∶0.1，v∶v，磷酸调pH 3.0）为流动相；荧光检测波长：激发波长380 nm，发射波长550 nm。

结果：人血浆中CPT-11和SN-38线性范围均为3~1000 ng·mL-1，定量下限为3 ng·mL-1；准确度分别是98.5%和100.0%；回收率分别是83.8%和84.3%。

结论：本方法可靠、简便、快速，可为伊立替康个体化给药提供参考。

%Objective: To determine irinotecan (CPT-11) and its active metabolite 7-ethyl-10-hydroxy-camptothecin (SN-38) in plasma of patients with colorectal cancer by high performance liquid chromatography coupled with fluorescence detection and to evaluate the dosage regimen by genotype information. Methods:Irinotecan and metabolites were detected in plasma. The internal standard was 2μg·mL-1 10-hydroxycamp-tothecin. Protein in plasma was precipitated with 10% perchloric acid before acidification with 10% perchloric acid. Separation of the compounds was achieved using anAgilent ZORBAX Eclipse C8 (4.6 mm×150 mm, 5μm) analytical column. The elution was performed with a mobile phase of 0.05 mol·L-1 sodium dihydrogen phosphate solution -acetonitrile (75∶25, v∶v) con taining 0.1% triethylamine. The fluorescence detector excitation and emis-sion wavelengths were set at 380 and 550 nm, respectively. Results: The linear ranges for CPT-11 and SN-38 were 3-1000 ng·mL-1. The limits of quantification of CPT-11 and SN-38 were 3 ng·mL-1. The average accuracy of CPT-11 and SN-38 were 98.5% and 100.0%; the average recoveries were 83.8% and 84.3%. Conclusion: This method is reliable, convenient and efficient, which can provide reference for individualized drug administration.【总页数】4页(P267-270)【作者】鞠晓宇;罗雪梅;葛卫红;王友群【作者单位】中国药科大学，南京 210009;南京大学医学院附属鼓楼医院，南京210008;南京大学医学院附属鼓楼医院，南京 210008;中国药科大学，南京210009【正文语种】中文【中图分类】R969.1【相关文献】1.HPLC法测定血浆中伊立替康及其代谢产物SN-38、SN-38G浓度及方法学研究[J], 汪皖青;黄晨蓉2.反相高效液相色谱法测定血浆中阿米替林及rn其代谢物去甲替林的总浓度和游离浓度 [J], 李金恒;许劲秋;曹晓梅;陈东阳3.高效液相色谱法测定癫痫患者血浆中奥卡西平活性代谢物的浓度及其血药浓度与疗效关系评价 [J], 张全英;徐文俊;俞蕴莉4.高效液相色谱法测定大鼠血浆中5，7，3’-三乙酰橙皮素活性代谢物橙皮素的浓度 [J], 秦娣;李俊;李荣;黄艳;任丹阳;陈昭琳5.反相高效液相色谱法测定利培酮及其活性代谢物的血药浓度 [J], 孟珺;何光明;刘丽娟因版权原因，仅展示原文概要，查看原文内容请购买。

tbd储存条件 -回复

tbd储存条件-回复TBD储存条件指的是To Be Determined（待定）储存条件，即暂时未确定的储存要求。

在某些情况下，尤其是在进行新产品开发或研究项目时，可能需要进行特定物品的储存，但对于储存条件，还没有确切的要求或指导方针。

本文将探讨TBD储存条件的应用和管理，并提供一些可行的解决方案。

首先，TBD储存条件适用于各种不同类型的物品，包括生物样品、化学物品、食品、药品等。

这些物品可能具有不同的特性和储存需求，因此需要针对每种物品进行个别考虑。

此外，在某些情况下，可能需要对储存条件进行多个阶段的调整，以便在进一步研究或开发过程中满足不同的需求。

针对TBD储存条件的管理，我们建议采取以下步骤：第一步，确定物品的特性。

在建立储存条件之前，必须了解物品的特性，包括其化学成分、生物活性等。

这将有助于确定储存条件的关键因素，并确保物品的稳定性和完整性。

第二步，评估已有的储存条件。

有些情况下，可能已有一些相关的储存条件可以参考。

这些条件可能来源于相关的研究文献、制造商提供的建议，或者是其他实验室或组织的经验。

评估这些条件的可行性，可以为我们制定TBD储存条件提供一个基准。

第三步，进行初步实验。

基于物品的特性和已有储存条件的评估，可以进行一些初步实验，以确定可能的储存条件范围。

这些实验可能包括温度、湿度、光照等因素的变化，以及对物品进行周期性检查以评估其稳定性和完整性。

第四步，监测储存条件。

一旦初步实验完成，建议建立一个监测储存条件的系统。

这可以包括使用传感器、数据记录器或其他监测设备来记录关键的储存条件因素，如温度、湿度和光照。

这样可以及时发现任何异常情况，并采取相应的措施来调整储存条件。

第五步，定期维护和评估。

储存条件需要定期进行维护和评估，以确保其有效性和适应性。

这包括定期检查监测设备的功能、维护储存场所的整洁和适当处理过期物品。

此外，还应测试和验证储存条件是否满足TBD物品的需求。

在制定TBD储存条件时，还有一些其他的注意事项需考虑。

气相色谱法测定格列齐特中残留乙醇和N,N-二甲基甲酰胺的量

气相色谱法测定格列齐特中残留乙醇和N,N-二甲基甲酰胺的
量
孙红英;王本晓
【期刊名称】《药学研究》
【年(卷),期】2007(026)002
【摘要】目的建立格列齐特中残留乙醇和N,N-二甲基甲酰胺的测定方法.方法应用气相色谱法,氢火焰离子化检测器,检测器温度为250℃.结果乙醇的线性范围为0.128～1.02mg·ml-1,r=0.9997,回收率为98.9%,RSD=0.63%(n=6).N,N-二甲基甲酰胺的线性范围为43.8～175.2 μg·ml-1,r=0.9998,回收率为
98.2%,RSD=1.12%(n=6).样品中只检出乙醇.结论该方法简单、准确.
【总页数】3页(P88-90)
【作者】孙红英;王本晓
【作者单位】山东省医药工业研究所,济南,250100;山东省医药工业研究所,济南,250100
【正文语种】中文
【中图分类】R9
【相关文献】
1.气相色谱法测定氨磷汀原料药中N,N-二甲基甲酰胺残留量 [J], 姜彩端
2.顶空气相色谱法测定硫酸奈替米星中N,N-二甲基甲酰胺溶剂残留量 [J], 毛威
3.气相色谱法测定依诺肝素钠中N,N-二甲基甲酰胺的残留量 [J], 马志华;赵焕荣;
姬胜利
4.气相色谱法测定依诺肝素钠中N,N-二甲基甲酰胺的残留量 [J], 马志华;赵焕荣;姬胜利
5.气相色谱法测定头孢妥仑匹酯中N,N-二甲基甲酰胺残留量 [J], 王晨; 李东伟; 崔晨辉; 王晶; 王彦广
因版权原因，仅展示原文概要，查看原文内容请购买。

D-Dimer标准操作流程

D－二聚体标准操作流程目录1 目的2 检测原理3 产品信息4 试剂配制5 试剂保存和稳定性6 预防和警告7 样本收集和准备8 检测需要但试剂盒中未提供的耗材9 质量控制10定标11定标方法 (如需要)12操作流程13结果14 结果解释15程序局限性16 预期结果17 性能特征18 参考文献1 目的此程序提供在ACL™ 8000，ACL9000上使用HemosIL D-Dimer试剂用于D-二聚体检测的指导。

2 测试原理D-二聚体存在于因子XIIIa交联纤维蛋白(XDP)纤溶酶降解过程中形成的可溶性衍生物中。

这些可溶性纤维蛋白降解产物包括一种原纤维蛋白原分子中没有的新抗原（D-二聚体结构），以及它的降解产物和可溶性纤维蛋白。

D-二聚体胶乳试剂是一种大小均一的聚苯乙烯乳胶颗粒悬浊液，这些乳胶颗粒上包被有对纤维蛋白可溶性衍生物中的D-二聚体结构具有高度特异性的单克隆抗体。

当含有D-二聚体的血浆与D-二聚体试剂盒中的乳胶试剂和反应缓冲液反应时，包被的乳胶颗粒会发生凝集。

凝集的程度与样本中D-二聚体浓度成正比，仪器通过检测405 nm 波长处，由凝集引起的透射光的减少进行测定（透射免疫比浊法）。

3 产品信息D-二聚体试剂盒（P/N 20008500）内含：胶乳试剂：4 瓶x 3 mL包被有鼠单克隆抗体 (MA-8D3)聚苯乙烯乳胶颗粒冻干悬浊液，内含牛血清白蛋白，缓冲液，稳定剂和防腐剂。

反应缓冲液：3瓶x9mL磷酸盐缓冲液，内含牛血清白蛋白，稳定剂和防腐剂。

D-二聚体定标液：2 瓶x 1 mL冻干溶液，为从人纤溶酶降解的纤维蛋白中部分纯化的D-二聚体。

内含牛血清白蛋白，缓冲液，稳定剂和防腐剂。

D-二聚体质控（P/N 20008610）试剂盒内含：低值质控： 5 瓶x 1 mL冻干溶液，为从人纤溶酶降解的纤维蛋白中部分纯化的D-二聚体。

内含牛血清白蛋白，缓冲液，稳定剂和防腐剂。

高值质控：5 瓶x 1 mL冻干溶液，为从人纤溶酶降解的纤维蛋白中部分纯化的D-二聚体。

MEDDEV 2 12-2 Chinese

EUROPEAN COMMISSION 欧盟委员会DG ENTERPRISE DG企业Directorate G 董事会GUnit 4 - Pressure Equipment, Medical Devices, Metrology第4单元-压力设备、医疗器械、计量学医疗器械指南该指南是指实施医疗器械EC指令中所遇到问题的系统指南中的一个。

这些指令与指南之间没有法律效益的关联。

这些指南是通过与各个利益方（包括主管当局，委员会服务机构，行业以及其他利益相关方）进行详尽的征询后谨慎起草的，在这个过程中，草稿有被传阅，相关的建议在文件中加以采纳。

因此，此文件体现了医疗器械各相关方代表的立场。

CEC 临床评估小组5月18日, 2004年医疗器械指令之上市后临床跟踪前言：PMCF的基本原因和目标本文件的目的是指为制造商和通告机构就如何执行PMCF, 和履行上市后监督义务提供指导性意见。

参照医疗器械指令附录II 3. 1, 附录IV 3. 附录V 3, 附录VI 3.1 附录VII 4 (增加参阅AIMDD)。

虽然临床证据是上市前符合性评定程序的基本要素，但重要的是要认识到，这些上市前临床调查存在局限性。

虽然在上市前阶段已经收集了广泛的数据，但是并不能保证制造商能够察觉到不常见的并发症或问题，而这些问题只有在医疗器械被大范围的使用和长期运行后才会显现。

作为医疗器械制造商的质量体系，或上市后监督体系的一个部分，关键就是需识别和调查销售后的医疗器械在使用过程中所具有的风险。

制造商应建立上市后监督系统，并且对每一个产品或产品类都应有明确的PMS（上市后监督）策划。

因此，选择PMCF(上市后临床跟踪)看起来是实现此目的的一个方法。

通过建立一个长期的安全跟踪评审程序和侦查一些可能出现的风险，它可以使病人获得新的疗法，而这些风险仅仅依赖上市前的临床调查（仅仅要求相对很短的时间跟踪）和根据产品经验或产品警惕性都是不能完全充分地察觉到的。