The-MIQE-Guidelines-MIQE指南

Revision of the EU GMP Guide Annex 11 "Computerised Systems" -Presentation of Concept Paper关于欧盟GMP指南附录11“计算机系统”的修订- 概念文件介绍The current EU GMP Guidance Annex 11 "Computerised Systems" has been in force since 2011. It has been discussed for a long time to revise this annex in order to meet current technological and regulatory developments. On 16 November 2022, the EMA (European Medicines Agency) published a 5-page "Concept-Paper on the revision of Annex 11 of the guidelines on Good Manufacturing Practice for medicinal products -Computerised Systems". Comments on this concept paper can be submitted until 16 January 2023.当前的欧盟GMP指南附录11“计算机化系统”自2011年起就已经生效。

关于修订该附录以反映最新的技术和法规发展的讨论，已经持续了很长一段时间。

2022年11月16日，EMA（欧洲药品管理局）发表了一份长达5页的“关于修订药品良好生产规范指南附录11-“计算机化系统”的概念文件”。

有关此概念文件的评论可以持续提交，截止到2023年1月16日。

Step 1: Sample Preparation & Nucleic Acid IsolationFor great results, use (click product names to learn more):Roche High Pure RNA Isolation KitRoche High Pure FFPET RNA Isolation KitRoche High Pure miRNA Isolation KitRoche RealTime ready Cell Lysis KitFrom which source (animal, organ, tissue) does the examined material originally come from? Which volume or mass or cell number was used for nucleic acid preparation?My MIQE Guide*Empowering results that matter Sponsored by Roche Applied Science Experiment title:Performed by:Date:Institution:Experimental design: How did you choose and set up your study (number of treated samplesand controls)Handling: Which tools or methods were used to obtain and process the primary samples (e.g., micro-dissection, macrodissection)?Method of processing and preservation: How was the sample treated and stored?If frozen – how and how quickly?If fixed – with what, and how quickly?If stored for longer: how and how long? (especially for FFPE samples)Extraction method:Which kit or instrument was used to extract/isolate the DNA/RNA from the starting material? Roche High Pure RNA Isolation Kit, High Pure FFPET RNA Isolation Kit, High Pure miRNA Isolation Kit, RealTime ready Cell Lysis Kit, or other (Please specify)Was the vendor’s protocol modified (If Yes, when, and how? e.g. by using additives)Did you do a DNAse or RNAse treatment? (If Yes, when?)Did you check for nucleic acid purity and integrity? If Yes: By using which instrument and method? What was the resulting purity (A260/A280)? What was the resulting yield? If No: Why not?Did you check for the presence of PCR inhibitors? If Yes: By using what (e.g. Cq dilutions, spike or other (please specify)If No: Why not?Final storage solution (e.g., buffer, H2O) for the purified total RNA:Storage time and temperature of the purified total RNA before use in RT-qPCR:Step 2:Reverse TranscriptionFor optimal results, use:Roche Transcriptor First Strand cDNA Synthesis KitRoche Transcriptor Universal cDNA MasterAmount of RNA and reaction volume:Priming oligonucleotide (if using gene specific primers) and concentration: Reaction temperature and time:Manufacturer of reverse transcription reagent(s) and catalogue number(s): Reverse transcriptase type and used concentration:Storage conditions of cDNA:Step 3:PCR Amplification and AnalysisFor best results, use:LightCycler® 480 Probes MasterFastStart Essential DNA Probes MasterFastStart Universal Probe Master (Rox)Target sequence and amplicon information: Target gene database sequence accession number:Location of amplicon:Amplicon length:Result of in silico specificity screen (BLAST, etc.):Information on pseudogenes, retropseudogenes or other homologs: Secondary structure analysis of amplicon:Determined by which method?Location of each primer relative to exons or introns (if applicable): Targeted splice variants:RTPrimerDB Identification Numbers: Manufacturer of oligonucleotides: Purification method:For probe-based assays: Probe type:qPCR reaction conditionsReaction volume and amount of cDNA/DNA per reaction: Primer, (probe), Mg2+ and dNTP concentrations: Polymerase identity:Buffer/kit manufacturer and identity (e.g., catalog number)Manufacturer and catalog number of plates or tubes and catalog number:Complete thermocycling parameters:Reaction setup: Was it manual or robotic? If robotic: Using which robot?Equipment: Which Real-Time PCR instrument was used? (Which Roche LightCycler® System or other (please specify)?)Validation of qPCR runs:Are you running a multiplex assay? If yes, please describe efficiency and limit of detection foreach assay:How did you check for specificity of amplification for each target (e.g., on a gel, by sequencing, melt-ing curve analysis or digest):For SYBR Green I assays: Cq of the non-template control reaction:Standard curve characteristics (slope and y-intercept):How many replicates did you use to establish the standard curve?(xx replicates per standard concentration)What was the lower and the upper limit of the standard curve?PCR efficiency calculated from slope:Confidence interval for PCR efficiency or standard error:r2 of standard curve:Information on linear dynamic range:Cq variation at lower limit: Confidence intervals throughout range:Evidence for limit of detection:How many reactions per run were used for controls? (please specify positive and negative controls, controls without template and No RT controls, e.g. Positive controls: 3 reactions in 5 replicates per 96 well plate)Data analysis:Vendor software: Which software type, version and algorithm provided by the PCR machine supplier was used to analyze the data?Specialist software: Which (if any) additional software was used? Self-developed algorithms,or other (please specify)Normalisation: Which reference gene(s) were used to calculate the relative expression of the studied genes?What was the reason for choosing these particular genes?Which algorithm (e.g., geNorm, bestkeeper, normfinder) was used to normalize for reference gene(s)Which principle was used for Cq calling?What was the number and of biological replicates used?How was their concordance?How many technical replicates were used, and at which step (RT or qPCR)? What was the observed repeatability (intra-assay variation)?What was the observed reproducibility (inter-assay variation, %CV)The MIQE guidelines empower results that truly matter. And so does Roche.Visit to discover all the materials you need for truly remarkable research results.* modified based on the list in the original MIQE guidelines publication with permission of the MIQE authors.For life science research only. Not for use in diagnostic procedures. LIGHTCYCLER and FASTSTART are trademarks of Roche.All other product names and trademarks are the property of their respective owners. NOTICE: This product may be subject to certain use restrictions. Before using this product, please refer to the Online Technical Support page () and search under the product number or the product name, whether this product is subject to a license disclaimer containing use restrictions.Published byRoche Diagnostics GmbH Sandhofer Straße 116 68305 Mannheim Germany© 2013 Roche Diagnostics. All rights reserved.*********** 1012。

New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)新版实体瘤疗效评价标准：修订的RECIST指南（1.1版本）Abstract摘要Background背景介绍Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics: both tumour shrinkage (objective response) and disease progression are useful endpoints in clinical trials. Since RECIST was published in 2000, many investigators, cooperative groups, industry and government authorities have adopted these criteria in the assessment of treatment outcomes. However, a number of questions and issues have arisen which have led to the development of a revised RECIST guideline (version 1.1). Evidence for changes, summarised in separate papers in this special issue, has come from assessment of a large data warehouse (>6500 patients), simulation studies and literature reviews.临床上评价肿瘤治疗效果最重要的一点就是对肿瘤负荷变化的评估：瘤体皱缩（目标疗效）和病情恶化在临床试验中都是有意义的判断终点。

药品共线生产质量管理指南英文English answer:Quality Management Guidelines for Co-line Production of Pharmaceutical Products.Introduction.Co-line production is a manufacturing process in which multiple products are produced on the same production line. This can be a cost-effective way to produce products, butit also poses some unique challenges to quality management.Quality Management System.The quality management system (QMS) for co-line production must be designed to ensure that all products are produced in accordance with their respective specifications. The QMS should include the following elements:A quality policy that defines the company's commitment to quality.A quality manual that describes the QMS.Standard operating procedures (SOPs) that describe how specific processes are to be performed.A quality assurance (QA) program to monitor and audit the QMS.A quality control (QC) program to test products and ensure that they meet specifications.Product Development.The product development process for co-line production must be carefully managed to ensure that products are compatible with each other and with the production line. The following steps should be taken during product development:Conduct a risk assessment to identify potential risks associated with co-line production.Develop a co-line production plan that outlines how products will be produced on the same line.Validate the co-line production plan to ensure that it is effective.Conduct a stability study to ensure that products are stable when produced on the same line.Manufacturing.The manufacturing process for co-line production mustbe carefully controlled to ensure that products are produced in accordance with their respective specifications. The following steps should be taken during manufacturing:Use dedicated equipment for each product.Clean and sanitize equipment between products.Follow SOPs for each process.Inspect products at critical control points.Test products to ensure that they meet specifications.Quality Assurance.The QA program for co-line production must be designedto monitor and audit the QMS to ensure that it is effective. The following steps should be taken during QA:Conduct regular audits of the QMS.Review product quality data.Investigate and resolve any quality issues.Quality Control.The QC program for co-line production must be designedto test products and ensure that they meet specifications. The following steps should be taken during QC:Test products at critical control points.Conduct stability testing.Release products for distribution only if they meet specifications.Conclusion.Co-line production can be a cost-effective way to produce pharmaceutical products, but it also poses some unique challenges to quality management. By following the guidelines outlined in this document, companies can ensure that they produce safe and effective products while minimizing the risk of cross-contamination and other质量问题.中文回答：药品共线生产质量管理指南。

MIQE指南范文MIQE（Minimum Information for Publication of Quantitative Real-Time PCR Experiments）指南是一个旨在提高实时定量PCR（qPCR）实验的透明度和可重复性的指南。

下面是一篇关于MIQE指南的范文，字数超过1200字：Abstract:Introduction:Material and Methods:1. Sample Collection: Tissue samples from different organs were collected from ten healthy individuals. The samples were immediately frozen in liquid nitrogen to preserve RNA integrity.2. RNA Extraction: Total RNA was extracted from the tissue samples using the TRIzol reagent following the manufacturer's instructions. RNA concentration and quality were determinedusing a spectrophotometer.3. cDNA Synthesis: RNA samples were treated with DNase I to remove genomic DNA contamination. cDNA was synthesized using the SuperScript III Reverse Transcriptase kit following the manufacturer's protocol.5. qPCR Assay: qPCR amplifications were performed using the SYBR Green PCR Master Mix and the Applied Biosystems 7500 Real-Time PCR System. The cycling conditions consisted of an initialdenaturation at 95°C for 10 minut es, followed by 40 cycles of 95°C for 15 seconds and 60°C for 1 minute.6. Data Analysis: The cycle threshold (Ct) values were determined using the Applied Biosystems software. The relative expression levels of Gene X were calculated using the 2^-ΔΔCt method, with GAPDH as the reference gene.Results:1. RNA Concentration and Quality: The concentration and purity of the RNA samples were assessed using a spectrophotometer. The samples exhibited an A260/A280 ratioof >1.8, indicating high RNA purity.2. Primer Specificity and Efficiency: The primer specificity was confirmed by the presence of a single peak in the melting curve analysis and the absence of non-specific amplification products. The primer efficiency was determined using a standard curve, which exhibited a slope of -3.32, corresponding to an efficiency of 97.9%.Discussion:Conclusion:In conclusion, following the MIQE guidelines is crucial for conducting accurate and reproducible qPCR experiments. This study demonstrated the successful application of the MIQE guidelines in investigating the expression of Gene X in varioustissues and conditions. By adhering to these guidelines, we were able to obtain reliable data, contributing to a better understanding of gene expression regulation.。

MIQE指南范文MIQE指南是科研实验中遵循的一项质量标准，全称为“Minimum Information for Publication of Quantitative Real-Time PCR Experiments”，直译为“发表定量实时聚合酶链反应实验证据的最低信息要求”。

它是为了提高定量实时聚合酶链反应（qPCR）实验的质量与可重复性而制定的指南。

MIQE指南包含了一系列涵盖所有与qPCR实验相关的信息要求，以确保实验与结果的准确性和可重复性。

它提供了一个标准化的实验报告模板，研究人员可以按照这个模板来组织和记录他们的实验过程和结果。

MIQE指南也为实验室提供了一些推荐的实验操作规范和技术流程，以确保实验过程的一致性和标准化。

2.试剂和材料：需要提供准确的实验试剂和材料的详细信息，包括生产商、批号和纯度等。

3.实验设计和数据分析：需要提供实验的设计和数据分析方法，包括实验方案、控制组设置、技术重复次数等。

4.仪器和反应条件：需要提供所使用的qPCR仪器的详细信息，包括型号和硬件配置，还需要提供反应条件等信息。

5.正确性和灵敏度：需要提供实验中用于验证方法准确性和灵敏度的相关信息，例如限制性酶切、序列分析等。

6.结果和讨论：需要提供实验结果的详细信息，以及对结果的客观分析和讨论，包括重复性和统计学分析等。

MIQE指南的目标是确保qPCR实验在不同实验室之间的结果是可比较和复制的，有助于科学研究的可靠性和可重复性。

同时，MIQE指南也使得科学家能够更好地了解实验操作的细节，以便更好地理解和解释结果，并且可以帮助实验设计和分析方法的改进。

总之，MIQE指南是为了提高定量实时聚合酶链反应实验的质量和可重复性而制定的一项质量标准指南。

它要求研究人员提供详细的实验描述和结果分析，以确保实验和结果的准确性和可比较性。

MIQE指南对于qPCR实验的标准化和科学研究的可靠性和可重复性具有重要意义。

EUROPEAN COMMISSIONHEALTH AND CONSUMERS DIRECTORATE-GENERALHealth Systems and ProductsMedicinal Products - Quality, safety and efficacyBrussels,SANCO/AM/sl/ddg1.d.6(2012)860362EudraLexThe Rules Governing Medicinal Products in the European UnionVolume 4EU Guidelines forGood Manufacturing Practice forMedicinal Products for Human and Veterinary UseChapter 1Pharmaceutical Quality SystemLegal basis for publishing the detailed guidelines: Article 47 of Directive 2001/83/EC on the Community code relating to medicinal products for human use and Article 51 of Directive 2001/82/EC on the Community code relating to veterinary medicinal products. This document provides guidance for the interpretation of the principles and guidelines of good manufacturing practice (GMP) for medicinal products as laid down in Directive 2003/94/EC for medicinal products for human use and Directive 91/412/EEC for veterinary use.Status of the document: revision 3Reasons for changes: Amendments to the text of Chapter 1 have been made in order to align with the concepts and terminology described in the ICH Q10 tripartite guideline on Pharmaceutical Quality System. The title of the chapter itself is also changed accordingly.Deadline for coming into operation: 31 January 2013Commission Européenne, B-1049 Bruxelles / Europese Commissie, B-1049 Brussel – Belgium. Telephone: (32-2) 299 11 11PrincipleThe holder of a Manufacturing Authorisation must manufacture medicinal products so as to ensure that they are fit for their intended use, comply with the requirements of the Marketing Authorisation or Clinical Trial Authorisation, as appropriate and do not place patients at risk due to inadequate safety, quality or efficacy. The attainment of this quality objective is the responsibility of senior management and requires the participation and commitment by staff in many different departments and at all levels within the company, by the company’s suppliers and by its distributors. To achieve this quality objective reliably there must be a comprehensively designed and correctly implemented Pharmaceutical Quality System1 incorporating Good Manufacturing Practice and Quality Risk Management. It should be fully documented and its effectiveness monitored. All parts of the Pharmaceutical Quality System should be adequately resourced with competent personnel, and suitable and sufficient premises, equipment and facilities. There are additional legal responsibilities for the holder of the Manufacturing Authorisation and for the Qualified Person(s).The basic concepts of Quality Management, Good Manufacturing Practice and Quality Risk Management are inter-related. They are described here in order to emphasise their relationships and their fundamental importance to the production and control of medicinal products.Pharmaceutical Quality System11.1 Quality Management is a wide-ranging concept, which covers all matters, which individually or collectively influence the quality of a product. It is the sum total of the organised arrangements made with the objective of ensuring that medicinal products are of the quality required for their intended use. Quality Management therefore incorporates Good Manufacturing Practice.1.2 GMP applies to the lifecycle stages from the manufacture of investigational medicinal products, technology transfer, commercial manufacturing through to product discontinuation. However the Pharmaceutical Quality System can extend to the pharmaceutical development lifecycle stage as described in ICH Q10, which while optional, should facilitate innovation and continual improvement and strengthen the link between pharmaceutical development and manufacturing activities. ICH Q10 is reproduced in Part III of the Guide and can be used to supplement the contents of this chapter.1.3 The size and complexity of the company’s activities should be taken into consideration when developing a new Pharmaceutical Quality System or modifying an existing one. The design of the system should incorporate appropriate risk management principles including the use of appropriate tools. While some aspects of the system can be company-wide and others site-specific, the effectiveness of the system is normally demonstrated at the site level.1 Art 6 of Directives 2003/94/EC and 91/412/EEC require manufacturers to establish and implement an effective pharmaceutical quality assurance system. The term Pharmaceutical Quality System is used in this chapter in the interests of consistency withICH Q10 terminology. For the purposes of this chapter these terms can be considered interchangeable.1.4 A Pharmaceutical Quality System appropriate for the manufacture of medicinal products should ensure that:(i) Product realisation is achieved by designing, planning, implementing,maintaining and continuously improving a system that allows the consistent delivery of products with appropriate quality attributes;(ii) Product and process knowledge is managed throughout all lifecycle stages;(iii) Medicinal products are designed and developed in a way that takes account of the requirements of Good Manufacturing Practice;(iv) Production and control operations are clearly specified and Good Manufacturing Practice adopted;(v) Managerial responsibilities are clearly specified;(vi) Arrangements are made for the manufacture, supply and use of the correct starting and packaging materials, the selection and monitoring of suppliers and for verifying that each delivery is from the approved supply chain;(vii) Processes are in place to assure the management of outsourced activities.(viii) A state of control is established and maintained by developing and using effective monitoring and control systems for process performance and product quality.(ix) The results of product and processes monitoring are taken into account in batch release, in the investigation of deviations, and, with a view to taking preventive action to avoid potential deviations occurring in the future.(x) All necessary controls on intermediate products, and any other in-process controls and validations are carried out;(xi) Continual improvement is facilitated through the implementation of quality improvements appropriate to the current level of process and product knowledge.(xii) Arrangements are in place for the prospective evaluation of planned changes and their approval prior to implementation taking into account regulatory notification and approval where required;(xiii) After implementation of any change, an evaluation is undertaken to confirm the quality objectives were achieved and that there was no unintended deleterious impact on product quality;(xiv) An appropriate level of root cause analysis should be applied during the investigation of deviations, suspected product defects and other problems.This can be determined using Quality Risk Management principles. In caseswhere the true root cause(s) of the issue cannot be determined, considerationshould be given to identifying the most likely root cause(s) and to addressingthose. Where human error is suspected or identified as the cause, this shouldbe justified having taken care to ensure that process, procedural or system-based errors or problems have not been overlooked, if present. Appropriatecorrective actions and/or preventative actions (CAPAs) should be identifiedand taken in response to investigations. The effectiveness of such actionsshould be monitored and assessed, in line with Quality Risk Management principles.(xv) Medicinal products are not sold or supplied before a Qualified Person hascertified that each production batch has been produced and controlled in accordance with the requirements of the Marketing Authorisation and any other regulations relevant to the production, control and release of medicinalproducts;(xvi) Satisfactory arrangements exist to ensure, as far as possible, that themedicinal products are stored, distributed and subsequently handled so thatquality is maintained throughout their shelf life;(xvii) There is a process for self-inspection and/or quality audit, which regularly appraises the effectiveness and applicability of the PharmaceuticalQuality System.1.5 Senior management has the ultimate responsibility to ensure an effective Pharmaceutical Quality System is in place, adequately resourced and that roles, responsibilities, and authorities are defined, communicated and implemented throughout the organisation. Senior management’s leadership and active participation in the Pharmaceutical Quality System is essential. This leadership should ensure the support and commitment of staff at all levels and sites within the organisation to the Pharmaceutical Quality System.1.6 There should be periodic management review, with the involvement of senior management, of the operation of the Pharmaceutical Quality System to identify opportunities for continual improvement of products, processes and the system itself. 1.7 The Pharmaceutical Quality System should be defined and documented. A Quality Manual or equivalent documentation should be established and should contain a description of the quality management system including management responsibilities.Good Manufacturing Practice for Medicinal Products1.8 Good Manufacturing Practice is that part of Quality Management which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the Marketing Authorisation, Clinical Trial Authorisation or product specification. Good Manufacturing Practice is concerned with both production and quality control. The basic requirements of GMP are that:(i) All manufacturing processes are clearly defined, systematically reviewed inthe light of experience and shown to be capable of consistently manufacturingmedicinal products of the required quality and complying with their specifications;(ii) Critical steps of manufacturing processes and significant changes to the process are validated;(iii) All necessary facilities for GMP are provided including:• Appropriately qualified and trained personnel;• Adequate premises and space;• Suitable equipment and services;• Correct materials, containers and labels;• Approved procedures and instructions, in accordance with thePharmaceutical Quality System;• Suitable storage and transport;(iv) Instructions and procedures are written in an instructional form in clear and unambiguous language, specifically applicable to the facilities provided;(v) Procedures are carried out correctly and operators are trained to do so;(vi) Records are made, manually and/or by recording instruments, during manufacture which demonstrate that all the steps required by the defined procedures and instructions were in fact taken and that the quantity and quality of the product was as expected.(vii) Any significant deviations are fully recorded, investigated with the objective of determining the root cause and appropriate corrective and preventive action implemented;(viii) Records of manufacture including distribution which enable the complete history of a batch to be traced are retained in a comprehensible and accessible form;(ix) The distribution of the products minimises any risk to their quality and takes account of Good Distribution Practice;(x) A system is available to recall any batch of product, from sale or supply;(xi) Complaints about products are examined, the causes of quality defects investigated and appropriate measures taken in respect of the defective products and to prevent reoccurrence.Quality Control1.9 Quality Control is that part of Good Manufacturing Practice which is concerned with sampling, specifications and testing, and with the organisation, documentation and release procedures which ensure that the necessary and relevant tests are actually carried out and that materials are not released for use, nor products released for sale orsupply, until their quality has been judged to be satisfactory. The basic requirements of Quality Control are that:(i) Adequate facilities, trained personnel and approved procedures areavailable for sampling and testing starting materials, packaging materials,intermediate, bulk, and finished products, and where appropriate for monitoring environmental conditions for GMP purposes;(ii) Samples of starting materials, packaging materials, intermediate products, bulk products and finished products are taken by approved personnel and methods;(iii) Test methods are validated;(iv) Records are made, manually and/or by recording instruments, which demonstrate that all the required sampling, inspecting and testing procedures were actually carried out. Any deviations are fully recorded and investigated;(v) The finished products contain active ingredients complying with the qualitative and quantitative composition of the Marketing Authorisation or clinical trial authorisation, are of the purity required, and are enclosed within their proper containers and correctly labelled;(vi) Records are made of the results of inspection and that testing of materials,intermediate, bulk, and finished products is formally assessed against specification. Product assessment includes a review and evaluation of relevant production documentation and an assessment of deviations from specified procedures;(vii) No batch of product is released for sale or supply prior to certification bya Qualified Person that it is in accordance with the requirements of therelevant authorisations in accordance with annex 16;(viii) Sufficient reference samples of starting materials and products are retained in accordance with Annex 19 to permit future examination of the product if necessary and that the sample is retained in the final pack.Product Quality Review1.10 Regular periodic or rolling quality reviews of all authorised medicinal products, including export only products, should be conducted with the objective of verifying the consistency of the existing process, the appropriateness of current specifications for both starting materials and finished product, to highlight any trends and to identify product and process improvements. Such reviews should normally be conducted and documented annually, taking into account previous reviews, and should include at least:(i) A review of starting materials including packaging materials used in theproduct, especially those from new sources and in particular the review ofsupply chain traceability of active substances.(ii) A review of critical in-process controls and finished product results.(iii) A review of all batches that failed to meet established specification(s) andtheir investigation.(iv) A review of all significant deviations or non-conformances, their relatedinvestigations, and the effectiveness of resultant corrective and preventive actions taken.(v) A review of all changes carried out to the processes or analytical methods.(vi) A review of Marketing Authorisation variations submitted, granted or refused, including those for third country (export only) dossiers.(vii) A review of the results of the stability monitoring programme and anyadverse trends.(viii) A review of all quality-related returns, complaints and recalls and the investigations performed at the time.(ix) A review of adequacy of any other previous product process or equipmentcorrective actions.(x) For new marketing authorisations and variations to marketing authorisations, a review of post-marketing commitments.(xi) The qualification status of relevant equipment and utilities, e.g. HVAC,water, compressed gases, etc.(xii) A review of any contractual arrangements as defined in Chapter 7 to ensure that they are up to date.1.11 The manufacturer and, where different, marketing authorisation holder should evaluate the results of the review and an assessment made as to whether corrective and preventive action or any revalidation should be undertaken, under the Pharmaceutical Quality System. There should be management procedures for the ongoing management and review of these actions and the effectiveness of these procedures verified during self-inspection. Quality reviews may be grouped by product type, e.g. solid dosage forms, liquid dosage forms, sterile products, etc. where scientifically justified.Where the marketing authorisation holder is not the manufacturer, there should be a technical agreement in place between the various parties that defines their respective responsibilities in producing the product quality review.Quality Risk Management1.12 Quality risk management is a systematic process for the assessment, control, communication and review of risks to the quality of the medicinal product. It can be applied both proactively and retrospectively.1.13 The principles of quality risk management are that:i) The evaluation of the risk to quality is based on scientific knowledge,experience with the process and ultimately links to the protection of the patient ii) The level of effort, formality and documentation of the quality riskmanagement process is commensurate with the level of riskExamples of the processes and applications of quality risk management can be found inter alia in ICH Q9 which is reproduced in Part III of the Guide.。

acmg指南英文版## English Response.ACMG Guidelines for the Interpretation and Reporting of Sequence Variants.The American College of Medical Genetics and Genomics (ACMG) has developed guidelines to assist clinicians and laboratory professionals in the interpretation andreporting of sequence variants. These guidelines are based on the latest scientific evidence and are designed to ensure that patients receive accurate and consistent information about their genetic test results.The ACMG guidelines use a five-tiered system toclassify sequence variants:Pathogenic: A variant that is known to cause disease.Likely pathogenic: A variant that is likely to causedisease, but additional evidence is needed to confirm pathogenicity.Variant of uncertain significance (VUS): A variantthat cannot be classified as pathogenic or benign.Likely benign: A variant that is likely to be benign, but additional evidence is needed to confirm benignity.Benign: A variant that is known to be benign.The ACMG guidelines also provide specific criteria for classifying variants into each of these categories. These criteria include:Population frequency: The frequency of the variant in the general population.Functional impact: The predicted impact of the variant on the function of the gene.Computational predictions: The predictions ofcomputational algorithms that can assess the pathogenicity of variants.Segregation data: The pattern of inheritance of the variant in a family.Other available evidence: Any other information that can help to classify the variant, such as animal models or functional studies.The ACMG guidelines are a valuable tool for clinicians and laboratory professionals who are interpreting and reporting sequence variants. By using these guidelines, clinicians can ensure that patients receive accurate and consistent information about their genetic test results.## Chinese Response.ACMG序列变异解读和报告指南。

EUROPEAN COMMISSIONHEALTH AND CONSUMERS DIRECTORATE-GENERALPublic Health and Risk AssessmentPharmaceuticalsBrussels,SANCO/C8/AM/sl/ares(2010)1064587EudraLexThe Rules Governing Medicinal Products in the European UnionVolume 4Good Manufacturing PracticeMedicinal Products for Human and Veterinary UseChapter 4: Documentation第四章：文件Legal basis for publishing the detailed guidelines:Article 47 of Directive2001/83/EC on the Community code relating to medicinal products for human use and Article 51 of Directive 2001/82/EC on the Community code relating to veterinary medicinal products. This document provides guidance for the interpretation of the principles and guidelines of good manufacturing practice (GMP) for medicinal products as laid down in Directive 2003/94/EC for medicinal products for human use and Directive 91/412/EEC for veterinary use.立法基础：2001/83/EC法令第47款对人用药品的相关要求，2001/82/EC法令第51款兽用药相关的欧共体法规。

D esign and optimization of S YBR Green assaysThis guide is intended to help researchers design and optimize scientifically sound qPCR experiments with Applied Biosystems ™ SYBR ™ Green assays. These recommendations are consistent with the MinimumInformation for Quantitative Experiment (MIQE) guidelines. By following the steps in this guide, you may be more confident that experimental results are based on the concentrations of target sequences, without limitations or biases introduced by enzymes, reagents, and, most notably, assay design.Reverse transcription (RT)—beware of RT bias Nearly all reverse transcriptases have the potential to introduce RT bias. If this happens, the amount of cDNA will not be consistently proportional to the amount How to test for RT biasWHITE PAPER SYBR Green assaysFor qPCR measurement of relative gene expressionFigure 1. Experimental determination of RT bias. RT reactions were run on a dilution series of RNA. The resulting cDNA was used to construct qPCR standard curves. (A) The two qPCR standard curves are parallel for all concentrations, indicating no RT bias. (B) An example of RT bias is indicated by the oval. Constructing this RT-qPCR standard curve will reveal if you are introducing RT bias, and is an important check that should be done for eachexperimental assay. The standard curve will also indicate how much RNA you can use and maintain linearity for qPCR. If the purification scheme changes, the standard curve check should be repeated.RNA quantityC tRAS GAPDH6040200AB62.5 ng RNA cDNA cDNA cDNA cDNA125 ng RNA 250 ng RNA 500 ng RNAStep 1: Reverse-transcribe 2-fold dilutions of a known amount of RNAStep 2: Run a qPCR standard curve (Figure 1) for each assay and an endogenous control12of RNA in samples. When using relative quantitation methods, it is especially important to make sure that conclusions are based on the biological effects of your experimental treatments and not on limitations or bias of the reverse transcriptases.RNA quantity6040200RAS C tGAPDHSYBR Green assays, step 1: bioinformatics1. Obtain the sequence for the gene of interest, and select an exon-to-exon spanning region ~200 bp in length.2. Use a tool such as SNPmasker(bioinfo.ebc.ee/snpmasker/) to mask forsingle-nucleotide polymorphisms (SNPs). SNPmaskerwill highlight any SNPs that occur.Forward primerGood result: single peak is indicative of a single PCR product.Unfavorable result: multiple peaksindicative of more than one PCR product.SYBRGreen dye will bind to both products and produce a signal.R e v e r s e p r i m e rExample sequence for RASatacaaggatgcgtacagtacattcagacgaatggccgatagagc gcatatcgcgaacatcgcgcatatcgcgctaaagcgcctaagcg ggcctaaaaggctcttccgcaaacatatacgcgcagtgcgcgcttac gaaggattggccattaggattagcccgccaggggattgagagc cagcccagcttagctcgatcgaacgactacaggctacatatataac gccgaattagccaggattatgccagggggtaattcagacaacaaa ShortcutSee page 3 for information on how to eliminate all primer validation steps.SYBR Green assays, step 2: primer validation In primer validation, the objective is to find the rightconcentration of forward and reverse primers that will yield the lowest C t and create no primer-dimers.1. Run multiple qPCR reactions with 3 to 4 different concentrations of forward and reverse primers.Actual quantities may vary from the example below. The appropriate range of primer concentrations is determined by the master mix.2. Evaluate C t for each combination.3. Run a melting curve for each combination.If melting curve analysis shows primer-dimers, there are two options:–Start over with the bioinformatics.–Alter cycling temperatures to remove primer-dimers. However, this may result in assays that run with different cycling temperatures and so cannot be combined with other qPCR assays.3. To avoid specificity issues, utilize a tool likeRepeatMasker ( ) that will look for runs of Cs and Gs.4. Now take this qualified sequence and insert it into a primer design tool such as Primer3web(bioinfo.ut.ee/primer3/). This should give you multiple sets of forward and reverse primers. Pick several for step 5.5. Use the BLAST ™ tool for primers(/) to ensure that the primers chosen in step 4 are specific for your gene and unique to your species of interest. 6. Order your primers from /oligos .Estimated total bioinformatics time: 1–2 hours Estimated reagent usage: 0How to validate assay efficiency1. If necessary, reverse-transcribe RNA to cDNA.2. Run a 5-point standard curve, in triplicate, using 10-fold dilutions for both the target gene and a reference gene.3. Plot C t vs. concentration to generate a standard curve for both target and reference genes (using qPCRsoftware). Look for >90% efficiency (to use ΔΔC t ). Slope values for the target gene and the reference gene should be within 0.1 of each other.Shortcut to all design and optimization steps with TaqMan AssaysBioinformatics shortcut: Applied Biosystems ™ TaqMan ® Assays minimize the need for more bioinformatics,because each assay has undergone our extensive 7-layer bioinformatics process before it arrives at your bench.*SYBR Green assays, step 3: assay efficiencyThere are two primary methods of relative quantitation: relative standard curve, and comparative C t (ΔΔC t or ddC t ). The efficiency of the assay (ability to double the amount of PCR product every cycle) will determine which method can be used.Takes away 30 sample wells from each platePrimer validation shortcut: TaqMan Assays help avoid the need for primer validation, because the combination of primers and probe is so highly specific that your qPCR instrument should detect only your target of interest.Assay efficiency shortcut: TaqMan Assays are guaranteed to offer efficiencies of >90%.TaqMan Assays are affordableFor less than you think, you can order a 75-reactionTaqMan Assay and start running experiments immediately. When you consider all the time, reagents, and samples** required to optimize a single SYBR Green assay, TaqMan Assays offer tremendous value. This is especially true if you find it necessary to start over at any point of the SYBR Green assay design and validation process.TaqMan Assay guarantees:• S ensitivity: 10 copies • A ssay efficiency: >90%• D ynamic range: 7 logarithmic units (we have demonstrated 9)• E ase of use: all TaqMan Assays have the same cycling protocolsPowerTrack SYBR Green Master MixApplied Biosystems ™ PowerTrack SYBR ™ Green Master Mix is formulated for maximum real-time PCR specificity and reproducibility, and includes a tracking dye system to minimize pipetting errors.• Built-in two-color tracking dye system to help improve pipetting accuracy and reaction setup• Broad primer T m and primer concentrationcompatibility allows qPCR reaction setup flexibility with minimal optimization• Superior specificity and tight reproducibility in C t values over a broad dynamic range improve data quality • Compatible with Invitrogen ™ SuperScript ™ IV VILO ™ Master Mix reverse transcription for fast, reproducible results• Formulated with UNG and dUTP to preventcontamination of the reaction by carryover PCR products • Broad instrument compatibilityFor more information about PowerTrack SYBR Green Master Mix and additional SYBR Green master mix formulations, go to /sybr* For exclusions, please see the TaqMan Guarantee Terms and Conditions at /us/en/home/brands/taqman/taqman-guarantee/taqman-guarantee-terms-conditions.html ** 39 qPCR reactions (9 or more for primer validation and 30 for assay efficiency)For Research Use Only. Not for use in diagnostic procedures. © 2020 Thermo Fisher Scientific Inc. All rights reserved. All trademarks are the property of Thermo Fisher Scientific and its subsidiaries unless otherwise specified. TaqMan is a registered trademark of Roche Molecular Systems, Inc., used under permission and license. BLAST is a trademark of the National Library of Medicine. COL23862 0220F ind out more about TaqMan Assays at/taqmanOrdering information PowerTrack SYBR Green Master Mix, Mini Pack (1 mL)100 reactions A46012PowerTrack SYBR Green Master Mix, 1-Pack (1 x 5 mL)500 reactions A46109PowerTrack SYBR Green Master Mix, 2-Pack (2 x 5 mL)1,000 reactions A46110PowerTrack SYBR Green Master Mix, 5-Pack (5 x 5 mL)2,500 reactions A46111PowerTrack SYBR Green Master Mix, 10-Pack (10 x 5 mL)5,000 reactions A46112PowerTrack SYBR Green Master Mix, Bulk Pack (1 x 50 mL)5,000 reactionsA46113。

ICH指导原则文件目录（中英文）人用药品注册技术要求国际协调会（ICH）文件目录ICH的论题主要分为四类，因此ICH根据论题的类别不同而进行相应的编码分类：1. “Q”类论题：Q代表QUALITY，指那些与化工和医药，质量保证方面的相关的论题。

Q1/Q2...Q10都属于这类。

2. “S”类论题：S代表SAFETY，指那些与实验室和动物实验，临床前研究方面的相关的论题。

3. “E”类论题：E代表EFFICACY，指那些与人类临床研究相关的课题。

4. “M”类论题：M代表MULTIDISCIPLINARY, 指那些不可单独划入以上三个分类的交叉涉及的论题。

同时M又细分为5个小类：M1: 常用医学名词（Med DRA）M2: 药政信息传递之电子标准M3: 与临床试验相关的临床前研究时间的安排M4: 常规技术文件(CTD)M5: 药物词典的数据要素和标准一、ICH. 质量部分（Quality）稳定性1.Quality质量2.Q1: Stability稳定性3.Q1A(R2): Stability Testing of New Drug Substances and Products 新原料药和制剂的稳定性试验4.Q1B: Photostability Testing of New Drug Substances and Products 新原料药和制剂的光稳定性试验5.Q1C: Stability Testing for New Dosage Forms 新剂型的稳定性试验6.Q1D: Bracketing and Matrixing Designs for Stability Testing of Drug Substances and Drug Products原料药和制剂稳定性试验的交叉和矩阵设计 Q1E: Evaluation of Stability Data 稳定性数据的评估7.Q1F: Stability Data Package for Registration Applications in Climatic Zones III andIV在气候带III和IV，药物注册申请所提供的稳定性数据8.Q2: Analytical Validation分析验证9.Q2(R1): Validation of Analytical Procedures: Text and Methodology分析程序的验证：正文及方法论10.Q3: Impurities 杂质11.Q3A(R2): Impurities in New Drug Substances 新原料药中的杂质12.Q3B(R2): Impurities in New Drug Products (Revised Guideline) 新制剂中的杂质13.Q3C(R3): Impurities: Guideline for Residual Solvents 杂质：残留溶剂指南Impurities: Guideline for Residual Solvents (Maintenance) 杂质：残留溶剂指南(保留)PDE for Tetrahydrofuran (in Q3C(R3)) 四氢呋喃的日允许接触剂量PDE for N-Methylpyrrolidone (in Q3C(R3)) N-甲基吡咯烷酮的日允许接触剂量14.Q4: Pharmacopoeias药典15.Q4A: Pharmacopoeial Harmonisation 药典的协调16.Q4B: Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions药典内容的评估及推荐为用于ICH地区17.Q4B Annex1 Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regionson Residue on Ignition/Sulphated Ash General Chapter附录1 药典内容的评估及推荐为用于ICH地区关于灼烧残渣/灰分常规篇18.Q4B Annex2 Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regionson Test for Extractable Volume of Parenteral Preparations General Chapter附录2 药典内容的评估及推荐为用于ICH地区关于注射剂可提取容量测试常规篇19.Q4B Annex3 Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regionson Test for Particulate Contamination: Sub-Visible Particles General Chapter附录3 药典内容的评估及推荐为用于ICH地区关于颗粒污染物测试:不溶性微粒常规篇20.Q5: Quality of Biotechnological Products 生物技术制品质量21.Q5A(R1): Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin来源于人或者动物细胞系的生物技术产品的病毒安全性评估22.Q5B: Quality of Biotechnological Products: Analysis of the Expression Construct in Cells Used for Production of r-DNA Derived ProteinProducts生物技术产品的质量：源于重组DNA的蛋白质产品的生产中所用的细胞中的表达构建分析23.Q5C: Quality of Biotechnological Products: Stability Testing of Biotechnological/Biological Products生物技术产品的质量：生物技术/生物产品的稳定性试验24.Q5D: Derivation and Characterization of Cell Substrates Used for Production of Biotechnological/Biological Products用于生产生物技术/生物产品的细胞底物的起源和特征描述25.Q5E: Comparability of Biotechnological/Biological Products Subject to Changes inTheir Manufacturing Process基于不同生产工艺的生物技术产品/生物产品的可比较性26.Q6: Specifications规格27.Q6A: Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances (including decision trees) 质量规格：新原料药和新制剂的检验程序和可接收标准：化学物质(包括决定过程)28.Q6B: Specifications: Test Procedures and Acceptance Criteria for29.Biotechnological/Biological Products质量规格：生物技术/生物产品的检验程序和可接收标准30.Q7: Good Manufacturing Practices （GMP）31.Q7A: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients活性药物成份的GMP指南32.Q8: Pharmaceutical Development药物研发33.Annex to Q8Q8附录34.Q9: Quality Risk Management质量风险管理35.Q10: Pharmaceutical Quality System药物质量体系二、ICH.安全性部分(Safety) 致癌试验1.S1A Guideline on the Need for Carcinogenicity Studies of Pharmaceuticals 药物致癌试验的必要性2.S1B Testing for Carcinogenicity of Pharmaceuticals 药物致癌试验3.S1C(R2) Dose Selection for Carcinogenicity Studies of Pharmaceuticals药物致癌试验的剂量选择4.S1C’药物致癌试验的剂量选择的附件：补充剂量限度和有关注释遗传毒性5.S2(R1) Guidance on Genotoxicity Testing and Data Interpretation forPharmaceuticals Intended for Human Use 人用药物的遗传毒性试验和数据分析指导原则6.S2A药物审评遗传毒性试验的特殊性指导原则7.S2B遗传毒性：药物遗传毒性试验标准组合药代8.S3A Note for Guidance on T oxicokinetics: The Assessment of Systemic Exposurein Toxicity Studies 毒代动力学指导原则：毒性研究中全身暴露的评价9.S3B Pharmacokinetics: Guidance for Repeated Dose TissueDistribution Studies药代动力学：重复给药的组织分布研究指导原则慢性毒性10.S4Duration of Chronic T oxicity Testing in Animals (Rodent and Non RodentToxicity Testing) 动物慢性毒性试验的周期（啮齿类和非啮齿类）生殖毒性11.S5(R2) Detection of T oxicity to Reproduction for Medicinal Products andToxicity to Male Fertility (the Addendum dated November 1995 has beenincorporated into the core guideline in November 2005 )12.S5A药品的生殖毒性检测13.S5B雄性生育力毒性其他14.S6Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals 生物技术药品的临床前安全性试验15.S7A Safety Pharmacology Studies for Human Pharmaceuticals 人用药物的安全性药理研究16.S7B The Non-clinical Evaluation of the Potential for Delayed VentricularRepolarization (QT Interval Prolongation) by Human Pharmaceuticals人用药延迟心室复极化（QT间期延长）潜在作用的非临床评价指导原则17.S8Immunotoxicity Studies for Human Pharmaceuticals人类药品的免疫毒性研究18.S9 Nonclinical Evaluation for Anticancer Pharmaceuticals 抗癌药物的临床前评价19.S10 Photosafety Evaluation三、ICH.临床部分(Efficacy)1.E1The Extent of Population Exposure to Assess Clinical Safety for Drugs Intended for Long-T erm Treatment of Non-Life-Threatening Conditions 评价临床长期给药方案的安全性2.E2A Definitions and Standards for Expedited Reporting 快速报告的定义和标准3.E2B(R3) Data Elements for Transmission of Individual Case Safety Reports个体病例安全性报告传递的数据要素4.E2C Periodic Benefit-Risk Evaluation Report 上市药品定期安全性更新报告5.E2D Post-Approval Safety Data Management: Definitions and Standards for Expedited Reporting批准后安全性数据管理：快速报告的定义和标准6.E2E Pharmacovigilance Planning药物警戒计划7. E2F Development Safety Update Report8.E3Structure and Content of Clinical Study Reports 临床研究报告的结构与内容9.E4Dose-Response Information to Support Drug Registration 新药注册所需量-效关系的资料10.E5(R1)Ethnic Factors in the Acceptability of Foreign Clinical Data 对国外临床研究资料的种族因素的可接受性11.E6(R1) Good Clinical Practice: Consolidated Guideline 药品临床研究规范（GCP）一致性指导原则12.E7Studies in Support of Special Populations: Geriatrics 老年人群的临床研究13.E8General Considerations for Clinical Trials 临床试验的一般考虑14.E9Statistical Principles for Clinical Trials 临床试验统计原则15.E10Choice of Control Group and Related Issues in Clinical Trials 对照组的选择16.E11Clinical Investigation of Medicinal Products in the Pediatric Population 儿童人群的临床研究17.E12按治疗分类的各类药物临床评价E12 Principles for Clinical Evaluation of New Antihypertensive Drugs18.E14The Clinical Evaluation of QT/QT c Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs 非抗心律失常药物致QT/QT c间期延长及潜在心律失常作用的临床评价19.E15 Definitions for Genomic Biomarkers, Pharmacogenomics, Pharmacogenetics, Genomic Data and Sample Coding Categories20.E16 Biomarkers Related to Drug or Biotechnology Product Development: Context, Structure and Format of Qualification Submissions四、ICH.综合部分 (Multidisciplinary)1.M1医学术语Med DRA2.M2Electronic Transmission of Individual Case Safety Reports MessageSpecification (ICH ICSR DTD Version 2.1) companion document to E2B(R3)注册资料传递所需的电子代码3.M3Guidance on Nonclinical Safety Studies for the Conduct of Human ClinicalTrials and Marketing Authorization for Pharmaceuticals与临床研究有关的临床前研究的时间安排4.M4 Organisation of the Common Technical Document for the Registration ofPharmaceuticals for Human Use (Edited with Numbering and Section Header Changes, September 2002). Including the Annex : the Granularity Document(Revised November 2003).CTD（common technical document）（包括CTD、CTD-Q、CTD-S、CTD-E和eCTD）药品词汇的数据要素和标准5.M4Q (R1) The Common Technical Document for the Registration ofPharmaceuticals for Human Use: Quality (Edited with Numbering and Section Header Changes, September 2002)6.M4S (R2) The Common Technical Document for the Registration ofPharmaceuticals for Human Use: Safety (Edited with Numbering and SectionHeader Changes, September 2002)7.M4E (R1) The Common Technical Document for the Registration ofPharmaceuticals for Human Use: Efficacy (Edited with Numbering and Section Header Changes, September 2002)8.M7 Assessment and Control of DNA Reactive (Mutagenic) Impurities inPharmaceuticals to Limit Potential Carcinogenic Risk Reference:1. 《ICH 药品注册的国际要求》2. /doc/d6990802.html,3./doc/d6990802.html,/health/Health/yx/yao/20 07-08-07/6326.html。

猪源性成分检测方法验证分析石　旺，杨　冰，陈帅虎，何雅媛，何　浩*（湖南省产商品质量检验研究院，湖南长沙 410007）摘　要：目的：建立基于基因扩增方法检测食品中动物源性成分的验证方法，提升实验室人员基因扩增的检测能力。

方法：依据SB/T 10923—2012，分析猪源性成分的扩增效率、基质效应参数和实验室间能力比对结果。

结果：猪源性成分扩增效率E＞90%，检出限可以达到0.1 ng，实验室间能力比对样品3116A和3116B获得了满意结果。

结论：实验室条件满足SB/T 10923—2012中猪源性成分扩增要求。

关键词：基因扩增；方法验证；扩增效率；基质效应Validation and Analysis of Detection Methods for Pig DerivedIngredientsSHI Wang, YANG Bing, CHEN Shuaihu, HE Yayuan, HE Hao*(Hunan Provincial Institute of Product and Goods Quality Inspection, Changsha 410007, China) Abstract: Objective: To establish a validation method based on gene amplification for detecting animal derived components in food, and to enhance the detection ability of laboratory personnel in gene amplification. Method: According to SB/T 10923—2012, analyze the amplification efficiency, matrix effect parameters, and inter laboratory capability comparison results of pig derived components. Result: The amplification efficiency E of pig derived components was greater than 90%, and the detection limit could reach 0.1 ng. Satisfactory results were obtained in the inter laboratory capability comparison of samples 3116A and 3116B. Conclusion: The laboratory conditions meet the requirements for amplification of pig derived components in SB/T 10923—2012.Keywords: gene amplification; method verification; amplification efficiency; matrix effect近年来，因食品假冒伪劣、真伪难辨而产生的食品安全问题越来越多[1-2]。

Cell therapy products are like the rockstars of the medical world, offering new hope for treating a range of diseases from cancer to autoimmune disorders. But creating these products is no walk in the park - there are all sorts of quality management hurdles to ovee. This document is like the ultimate guidebook for manufacturers, giving them the keys to ensuring the top-notch quality and safety of their cell therapy products. It's like a roadmap to avoiding contamination, ensuring every product is as fabulous as the last, and ultimately, making sure every patient is cheering for a successful oue. So, let's dive in and rock the world of cell therapy production!细胞疗法产品类似于医学界的摇滚巨星，为治疗从癌症到自体免疫障碍等一系列疾病提供了新的希望。

但创造这些产品在公园里是无法走动的，这份文件就像制造商的终极指南，给了他们确保细胞治疗产品最高质量和安全的关键。

这就像一个避免污染的路线图，确保每件产品都和最后一件一样美妙，确保每个病人都为成功欢呼。

一、总有机碳（总氮）分析仪1、用途：适用于地表水、地下水、海水、废水、自来水、纯水、土壤、沉积物、泥浆、固废等样品中TOC/TN含量的检测分析；2、性能与技术指标2.1工作条件：环境温度-20～49℃；相对湿度10～90%；电源 220V，50Hz；2.2测定原理：样品在铂金催化剂作用下完全燃烧，并将样品中有机物完全转化为CO2 后通过静压浓度-NDIR（非色散红外检测器）检测定量；*2.3燃烧温度：680℃-1000℃铂金催化燃烧，温度可选，适应不同样品需求之后, 进*2.4检测器类型：TOC：静压浓度-NDIR（非色散红外检测）即样品氧化为CO2入非色散红外检测器（NDIR），通过载气加压让全部CO进入检测池，在压力保持平衡2时进行检测，保证结果的准确性；； TN:PMT化学发光检测器2.5测定项目：TOC/TN、TC-IC/TN、NPOC/TN，IC/TN；2.6分析时间：TOC:≤4min；TN:7-8min2.7测定范围：TOC：0-30000ppm；TN:0-2000ppm2.8检测限：≤50ppb；*2.9 颗粒物兼容性：0.8mm；2.10仪器检测精度：RSD≤1.5%；*2.11采用注射泵进样，进样量：100－2000μL（可变）；2.12采用气液分离器和渗透式干燥管双重除水技术进行水分去除；*2.13载气要求：配备高纯空气或高纯氧气；*2.14标配质量流量控制器（MFC）：可控检测池和系统的加压、流速；系统特性允许用户自行改变方法中的设置，无需流量调节阀和减压调节器；自动实现整体管路的泄漏测试；*2.15自动进样器在主机上部，一体化设计，节约实验室空间。

进样部件及无机吹扫部件必须可见，如注射泵、无机吹扫室、气液分离器等；*2.16燃烧炉安装在导轨上，方便更换燃烧管。

燃烧管为圆柱形设计，更换时无需借助工具便可拆卸，管内催化剂为Pt，填充方便；2.17具有自动样品吹扫功能；2.18IC预去除功能：主机内完成，内部注射器部件能够自动添加酸并进行吹扫；2.19具有自动稀释功能，稀释倍数：1－200倍；2.20具有智能稀释功能：当系统发现样品含量超过线性范围时，系统将自动稀释样品浓度至线性范围；*2.21具有自动标准曲线功能：根据线性浓度的要求，系统自动稀释溶液至最终浓度，减少了多次人工配置标准溶液带来的误差，同时提高分析效率；2.22软件允许客户编辑、上传和下载所有的参数和方法。