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迪伯达推销模式迪伯达公式是海因兹·姆·戈德曼根据自身推销经验总结出来的新公式，被认为是一种创造性的推销方法。
“迪伯达”是六个英文字母DIPADA的译音。
这六个英文字母分别为六个英文单词的第一个字母。
它们表达了迪伯达公式的六个推销步骤：第一步，准确地定义顾客的需要与愿望（Definition）。
第二步，鉴别推销品并与顾客需要结合起来（Identification）。
第三步，证实所推销的产品符合顾客的需要（Proof）。
第四步，促进顾客接受所推销的产品（Acceptance）。
第五步，激起顾客的购买欲望（Desire）。
第六步，促成顾客采取购买行动（Action）。
迪伯达公式较适用于：经销商设立，生产资料市场产品、老顾客及熟悉顾客、无形产品及开展无形交易（如保险、技术服务、咨询服务、信息情报、劳务市场等）、顾客属于有组织购买即单位购买者等产品或顾客的推销。
我们来举两例子来说明迪伯达公式的应用：案列1：业务员在东莞签订了一个经销商以后，该经销商迟迟不下单订货。
我觉得很奇怪，决定自己去拜访一下该经销商，了解一下问题所在，让该经销商把产品进过来，开始合作。
我决定先分辨他的真正需求，到其公司后先观察了一下他的公司，发现其经营的开关插座只有福田一个品牌，福田属于低端品牌，该公司没有经营中高端品牌，结合到东莞地区大量实体经济外迁，低端电工消费需求下降状况，我估计他的生意会陷入困难。
心里形成了一个谈判策略。
以下是我和经销商的对话：我：X总，我能向你提几个问题么？X总：可以，你有什么问题呢？我：东莞这几年实体经济外迁，对你批发业务有没有影响呢？X总：影响很大，销量下降了50%，我：实体经济外迁，出租房和工厂的需求下降，必然会使低端的电工市场容量萎缩，而你们的目标市场为低端市场，即使你们比以前更努力，也会事倍功半，销量必然受到影响，我猜的对吧？X总：对的。
我：那你们有什么对策：X总：我们的对策就是转型。
P.O. Box 3286 - Logan, Utah 84323, U.S.A. - Tel. (800) 729-8350 – Tel. (435) 755-9848 - Fax (435) 755-0015 - Section 1. Identification of the Substance/Mixture and the Company1.1 ProductIdentifierProduct Name: Sudan Black B Stain Kit (For Fat)Product Number: SBK-1, SBK-2, etc.1.2 Intended useEN: Laboratory reagent. For professional use only.DA: Laboratoriereagens. Kun til professionelt brug.DE: Laboratoriumreagens. Alleen voor professioneel gebruik.EL: Αντιδραστήριο εργαστηρίου. Για επαγγελματική χρήση μόνο.ES: Reactivo de laboratorio. Sólo para uso profesional.FR: Réactif de laboratoire. Pour un usage professionnel uniquement.IT: Laboratorio di reagente. Solo per uso professionale.NL: Laboratoriumreagens. Alleen voor professioneel gebruik.PT: Reagente de laboratório. Para uso profissional.SV: Laboratoriereagens. Endast för yrkesmässig användning.1.3 Details of thesupplier of thesafety data sheetManufacturer ScyTek Laboratories, Inc.Address 205 South 600 WestLogan, Utah 84321U.S.A.Phone Number 800-729-8350Fax Number 435-755-0015e-mail *****************Website 1.4 EmergencyTelephoneChemtrec (USA): 1-800-424-9300Section 2. Hazards Identification2.1 GHSClassificationSkin irritation (Category 2) – H315Eye irritation (Category 2) – H3192.2 LabelElementsPictogram(s):Signal word: WarningHazard statement(s): H315 – Causes skin irritationH319 – Causes serious eye irritationPrecautionary statement(s): P302+ P352 - IF ON SKIN: Wash with plenty of soap and waterP305 + P351 - IF IN EYES: Rinse cautiously with water forseveral minutes.P280 - Wear protective gloves, protective clothing, and eye/face protection.P.O. Box 3286 - Logan, Utah 84323, U.S.A. - Tel. (800) 729-8350 – Tel. (435) 755-9848 - Fax (435) 755-0015 - HEALTHFLAMMABILITYPHYSICAL HAZARDPERSONAL PROTECTIONPBT: This mixture does not contain any substances that are assessed to be a PBT.Section 3. Composition and Information on IngredientsSee components SDSSection 4. First Aid MeasuresSee components’ SDSSection 5. Fire Fighting MeasuresSee components’ SDSSection 6. Accidental Release MeasuresSee components’ SDSSection 7. Handling and Storage7.1 Precautions for safe handling.Avoid damaging kit.7.2 Conditions for safe storage, including any incompatibilities.Store in well ventilated area.Store at 15-30°C.7.3 Specific end use(s).See section 1.2Section 8. Exposure Controls / Personal ProtectionSee components’ SDSSection 9. Physical and Chemical Properties1P.O. Box 3286 - Logan, Utah 84323, U.S.A. - Tel. (800) 729-8350 – Tel. (435) 755-9848 - Fax (435) 755-0015 - See components’ SDSSection 10. Stability and ReactivitySee components’ SDSSection 11. Toxicological InformationSee components’ SDSSection 12. Ecological InformationSee components’ SDSSection 13. Disposal ConsiderationsSee components’ SDSSection 14. Transport Information – DOT IATA, IMDG, ADR, etc.14.1 UN Number Not dangerous goods14.2 UN Proper ShippingNameNot dangerous goods14.3 Transport HazardClass(es)Not dangerous goods14.4 Packing Group Not dangerous goods14.5 Environmental Hazards Marine Pollutant: No14.6 Special Precautions forUserNot applicable.Section 15. Regulatory Information15.1 Safety, Health and Environmental Regulations/Legislation Specific for the Substance or Mixture. Extremely HazardousSubstances; Section 355None of the components in this Kit are listed.Toxic Substances ControlAct; TSCAAll of the components in this Kit are listed.California Proposition 65 N/ARight To Know Components N/ASection 16. Other InformationThe above information is believed to be correct but does not purport to be all inclusive and shall be used only as a guide. ScyTek Laboratories shall not be held liable for any damage resulting from handling or from contact with the above product.。
美国FDA分析方法验证指南中英文对照2012-03-05 10:37I. INTRODUCTIONThis guidance provides recommendations to applicants on submitting analytical procedures, validation data, and samples to support the documentation of the identity, strength, quality, purity, and potency of drug substances and drug products.1. 绪论本指南旨在为申请者提供建议，以帮助其提交分析方法，方法验证资料和样品用于支持原料药和制剂的认定，剂量，质量，纯度和效力方面的文件。
This guidance is intended to assist applicants in assembling information, submitting samples, and presenting data to support analytical methodologies. The recommendations apply to drug substances and drug products covered in new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologics license applications (BLAs), product license applications (PLAs), and supplements to these applications.本指南旨在帮助申请者收集资料，递交样品并资料以支持分析方法。
这些建议适用于NDA，ANDA，BLA，PLA及其它们的补充中所涉及的原料药和制剂。
16Date of Issue WORLDSKILLS QUALITY ASSURANCE STANDARD Document No.TD16 Approved Technical Description – Industrial Electronics Revision1WorldSkills (International Vocational Training Organisation), by a resolution of the Technical Committee and in accordance with the Constitution, the Standing Orders and the Competition Rules, has adopted the following minimum requirements for trade No. 16 for the WorldSkills Competition:The effective date will be that date on which this document is issued, subject to approval by the Chairman of the Technical Committee.1Name and description of trade1.1The name of the trade is:Industrial Electronics1.2The Industrial Electronics Technician works in industrial or commercialenvironments and works with or studies electronics. This includes:- development- construction- design- measuring- testing- repair1.3This technical description must be known to every candidate.1.4In the event of any query or conflict within the technical descriptions, the Englishcopy will take precedence1.5Words implying masculine gender only shall include the feminine gender2Scope of work at WorldSkills Competitions2.1The practical work will test the competitors ability to:- assemble, adjust, commission, measure and test electronic equipment- carry out and document measurements on analogue and digital circuits- locate, document and repair faults in a given circuit- design or refine a design of a circuit, and construct using prototypeconstruction techniques2.2To solve theoretical tasks using mathematical and graphical methods to aTechnician Level2.3To redraw a circuit drawing schematic with Computer Aided Design.Competitors must bring their own laptop and software of their choice.3Competition Format for Practical Work3.1AssemblingAssemble a project that has to be from a kit of parts to the IPC-A-610 issue Cinternational acceptability of electronic assemblies. (Web page/main/ipca/htm. Each project should be able to fit a Euro cardstandard using DIN 41612 F64 or F32connectors, that will fit a standard backplane connector. Power points will be as follows: -A1C1+5v DigitalA2C2Digital GroundA15+5v AnalogC15+12v AnalogA16C16Analog groundA17-5v AnalogC17-12v AnalogA31C31Digital GroundA32C32+5v Digital3.2Measuring and TestingTo work with conventional measuring and testing equipment for AC, DC, digitaland analog electronics. To test, set, adjust and measure electronic components,modules and equipment. To record and analyse measured results. Boards willbe pre-built before the competition.3.3Fault Finding and RepairTo test, locate and replace faulty electronic components on a printed circuitboard, surface mount board or mixed technology board.All surface mountcomponents to have no more than four pins and Fault finding method/procedurewith results will be required. All boards will be pre-built before the competition.Each board will have at least three faults. Pin configurations and power supplywill be as 3.0.Competitors may bring their own measurement instruments.3.4Prototype DesignTo carry out a simple electronic design using given components to meet a givenspecification. Printed circuit boards should be pre-built. Resistors E24 series,0.25 watt to be available from host country.No more than 15 wire wrapconnections and no more 15 point to point connections will be required on thismodule. Pin configurations and power supply will be as 3.0.Competitors may bring their own measurement instruments.3.5The competition is modular and will be marked at the end of every module.3.6Time allowed for each module is as follows:Theory 2 hoursDrawing 2 hoursPrototype 4 hoursFault Finding 4 hoursMeasurement 4 hoursAssembly Project 3 + 3 hours4Theoretical Knowledge4.1To solve theoretical problems, using mathematical and graphical methods basedon the following:4.1.1Fundamental electronic principles:1. Basics of AC and DC technology.2. Two ports LRC networks, resistive networks with up to three meshes.3. RC oscillators.4.1.2Components in Electronics:Properties, behaviour, characteristics and application (elementary circuits) ofmechanically, electrically and physically adjustable components i.e.:-Resistors-Capacitors-Coils-Transformers-Diodes: rectifying diodes, switch diodes, zener diodes, capacitive diodes, PIN diodes-Trigger components: diac, triac, thyristor and uni-junction transistors.4.1.3Multistage and special amplifier circuits:Basic amplifier circuits (AC, DC and power amplifiers)Differential amplifiers/operational amplifiers.1. Ideal operational amplifier: (infinite input resistance, zero outputresistance and infinite open loop grain) Basic circuits with operationalamplifier, analogue adder and subtractor, differentiator, comparator,impedance transducer.2. Real operational amplifier: Offset voltage and offset current,compensation, common mode gain and rejection, temperature drift,frequency response.4.1.4Generators and Pulse shapers:1. Generators for sine wave voltage: RC, quartz, LC oscillator; wien bridgegenerator, phase generator.2. Pulse shaper: Schmitt trigger, differentiator, integrator.4.1.5Digital Electronics1. Basic logic gates.2. Level switching function, function table, pulse, diagram, circuit symbols(table in appendix).3. Properties of basic gates AND, OR, NOT, NAND, NOR, EXCLUSIVE OREXCLUSIVE NOR.4. Substituting basic NAND or NOR gates for basic gates.5. Creating switching functions from given circuits and vice versa.6. Making function table from circuit diagrams and switching functions.7. Simplifying switching networks using Karnaugh diagram or mathematicaltechniques.8. Flip-flops; RS Flip-flop, D Flip-flop, JK Master slave Flip-flop (especiallycounter circuits, shift register and frequency divider).9. Memory circuits, selection, addressing, and memory decoding volume.5Materials5.1ComponentsThe workshop master must ensure that the materials provided are completed,packed in bags and checked also for the power supply project, and range of E24,0.25w resistors from 10 ohm to 10 megohms is supplied. The host country willalso supply the back plane as per drawing –Refer Document 4.3/PD16 – Project Design Criteria5.2Other materials1. Graph paper A3 size2. Solder 60/40 type3. Approx. 5m bare wire (0.5mm diameter) per competitor4. Approx. 5m each of insulated wire (or standard wire) in five differentcolours for each competitor5. Binding/insulation tape6. Lacing string /Tie raps/heat shrink sleeving7. Hot-air fan for heat-shrink tubing5.5ClothingWork clothes must comply with relevant safety standards. Safety standardsrequire a minimum of safety glasses and covered footwear.6Workshop Installations6.1The working area should provide enough space for the competitors, experts(jury), measurement and repair area, material cupboards and wardrobes.6.2The general layout of the workshop venue will be as below, with sufficient spacefor the booth and for the competitors working area as defined in 6.3 below.Key to the layout above is:Please note that this is an example of the layout, and is not definitive. The minimum area requirements will be available.6.2.1General RequirementsThe working area should provide enough space for the competitors, expert’s (jury), measurement and repair area, material cupboards and wardrobes.Lockable cupboards must be provided for the safe keeping of the materials and the examination papers under the responsibility of the chief expert.The organizers will provide four sets of the following for the experts:1. 4 x Hot-air fan for heat-shrink tubing2. 2 x Magnifiers for experts x3 or x53. 2 x Computers4. One Laser printer6.3The personal working area for each competitor should be about 3m x 3m, andshall also allow for the equipment and machines specified in Sec. 6.4 below.6.4Measuring Instruments and Tester/ToolsThe organisers will provide the following for each competitor:1. 1x universal DVM2. 1x Function generator 1-50 MHz, sine, square, triangle3. 1x stabilized power supply (3-30V adjustable)4. Various connection cables (if necessary, coax cable with BNC plugs)5. 1x Bench Lamp6. 1x Electrostatic workstation7. 1x Calculator, non-progammableThe organizers will also provide a spare set of the above for the experts.6.5Competitors must bring all their own tools, including wire-wrapping equipment.Measurement instruments are optional.Each competitor may send his tools ahead to the host country in a light, sturdy and lockable toolbox. A complete list of the contents must accompany the toolbox for Customs clearance i6.5.1Unauthorised tools are not permitted. In case of doubt, the competitor must applyto the Jury in advance. Their decision will take into consideration technological progress and the aim of the competition.7Test Project Marking7.1The experts will decide together on the test projects, the marking criteria and thedimensional tolerances on forms 5, and 6, and they will prepare the marking list.Any Country who has a project submitted and his/her candidate gains a largerscore and all the other competitors have a low score, the average of all the lowscores will be awarded to the country competitor who submitted the project.7.2Marks:Perfect = 10 pointsVery good = 9 pointsGood = 8 pointsRather good = 7pointsSufficient = 6 pointsMedium = 5 pointsWeak = 4 pointsInsufficient = 3 pointsVery bad = 2 pointsZero = 1 point7.3RatingSection Item Maximum PointsA Theory10B Drawing10C Prototype22D Fault Finding22E Measurement22F Assembly Project15GH7.4Conversion to the 400 - 600 scale will be done by computer.8Competition Procedure8.1The competition will be worked on over all four days of the competition. Moduleswill be completed on each day for all competitors so that progressive markingcan take place, and for results to be made available each day.8.2Competitors will have time made available to familiarise themselves with materialand processes. Where processes are particularly difficult, the host country willprovide a subject matter expert to demonstrate the process and the competitorswill be given the opportunity to practice.8.3The competitors will be given all competition documents including the markingcriteria one hour prior to the commencement of the competition so that they maystudy the requirements8.4Prior to the start of the competition, each competitor will receive a detailedtimetable reflecting the timing for completion of modules.8.5Project Design, Selection and Documentation will be carried out as specified inAppendix 1PCB information is provided in Appendix 68.6Ballot Selection of Competitors Work Areas, Competition Notes and Timetable8.6.1For a total random selection procedure, the country codes should be placed inone bin and workbench numbers in another. Alphabetically the countrycompetitors will select one piece of paper from each, and this is then the startbench for that country.8.7The rules and procedures, and timetable specified in Appendix 2, 3 and 4 mustbe complied with.9Judging procedural requirements9.1The experts that attend the competition will be divided into marking groups todeal with each section of the marking criteria.9.2Every completed module will be marked on the same day in which it wascompleted.10General safety requirements10.1All competitors must use safety glasses when using any hand, power or machinetools or equipment likely to cause or create chips or fragments that may injurethe eyes10.2All competitors must wear appropriate clothing.10.3All machinery, equipment and safety clothing must comply with the safety rulesof the organising country.10.4Competitors must keep their workspace clear of obstacles and the floor spaceclean of material and equipment - any items likely to cause the competitor to trip,slip or fall.10.5Failure by the competitor to comply with safety directions or instructions mayincur penalties for safety.10.8Judges will wear the appropriate personal safety equipment when inspecting,checking or otherwise working with a competitor’s project.10.9Safety Checklist must be adhered to and is provided in Appendix 511Additional Documentation11.1The following additional documentation relates to this trade.•Nil at present11.2The following additional documentation relating to this trade has yet to be definedat the next WorldSkills Competition to be held in St Gallen in 2003.•Document TM16 – Trade Management Procedures•Document WS16 – Workshop Setup•Document PD16 – Project Design CriteriaTrade 16 Electronics - Competition ManagementThe following Countries will provide the following at the 2003 competition.Country AssemblyProject MeasuringandTestingFaultFindingandRepairDesign/PrototypeTheory1 Digital1AnalogDrawingBrazil X XCanada X X X Finland X X X Germany X X XJapan X X X Korea X X X Macao XLit X X XMorocco X X Portugal X X X X Singapore X X X Switzerland X XTaiwan x X X Tunisia x x XUnitedKingdomx x x x Project Selection GuidelinesAll competition presentations will be made in English and before any project is presented for selection they must be checked that they conform to the current rules of the world skills, and the current Technical Description. If the rules are not followed the project will not be considered for selection. All documentation must adhere to the world skills rules otherwise it will not be selected. The experts will form into a project group with other countries under the same heading. They will then select either one or a number of projects for the competition, as for the timetable as 3:7. Experts will then present their selection to the rest of the experts. Following everyone’s approval the experts will then agree a marking scheme for the project/ projects. When the competition begins, these experts manage and mark that aspect of the competition under guidance from the Chief Expert.Project DocumentationProject documentation must be brought to the competition on 3.5” floppy disc format,/CD in Microsoft Word. Where experts have used a drawing software. Experts should bring along the version of the drawing program software that they used. Paper copies should also be presented and where possible in three official languages. Where possible circuit diagrams will be used for all modules and project wording should be as brief as possible. All projects must include the following:-1. Short project brief2. Parts list3. Circuit diagram4. Data sheet pack5. Projects will only be accepted with softwareFirst Time CountriesAny Countries attending the competition for the first time should contact the Chief Expert via world skills who will then forward previous competition documentation and agree a project in advance for consideration.Competition Rules for Competitors while working on their Projects1. You must not talk to your own country expert or visitor without the presence of one other expert2. If you have a question raise your hand.3. You must not leave your workstation without permission, except to obtain wire etc from centrebench.4. If you feel ill or require anything, raise your hand.5. You may not leave the stand without an escort except at scheduled times for lunch and visitsto other stands.6. You must not touch any project other than your own.7. You may not touch any other competitors equipment.8. If you finish and leave your stand early, you must leave the stand.9. No use of mobile phones is permitted.10. No talking to any people outside the stand area while you are working on a project.Competition Timetable - Trade 16 Industrial ElectronicsDay 1Step Activity Start time Finish time 1Introduction by Chief judge9.009.159.1509.452Demonstration of assembly rack andpower supplies3Start assembly10.0013.00 4Lunch13.0014.00 5Continue with assembly of project14.0017.00 Total competition time 6.00 Day 2Step Activity Start time Finish time 1Drawing Introduction9.009.30 2Drawing/C programming9.3011.30 3Tour around venue and lunch11.3012.00 4Theory Introduction12.4513.00 5Theory13.0015.00 6Break15.0015.15 7Demonstration of Fault Finding one project15.1515.30 8Fault finding one15.3017.30 Total competition time 6.00 Day 3Step Activity Start time Finish time 1Introduction to Design Project9.0009.30 2Design & prototype09.3012.30 3Lunch12.3014.00 4Demonstration of fault finding project14.0014.15number 25Fault finding14.1516.15 6Tour around venue16.1517.00 Total competition time 5.00 Day 4Step Activity Start time Finish time9.009.151Demonstration of Measurement andTesting project2Measurement project9.1512.15 3Lunch12.1513.30 4Demonstration of C programming project13.3014.005 C programming project14.0016.00 Total competition time 5.00 Overall competition time22.00FAIRNESSAs part of World Skills each competition is required to have a fairness of competition rules for the experts, which are listed below for your comments.Before the competition startsAll experts are to be trustedExperts to believe in each other and their valuesEffective management of timeCommunicate both accurate and completeKeep communication with team members user-friendlyBe a good listenerAs a team we value the contributions of its membersReach early agreement and our goals and have contingency plansCreate a vision of success for other competitions to followWe will not make preformed judgementsRecognise issues early and open dialogue then explore for common groundIf you have a visitor to the stand he/she must not speak to the competitorsBe united in our decisionsAlways show a united front when dealing with the competitorsWhen the competitors arriveYou must not talk to your own country competitor or visitor without the presence of one otherexpertYou must not leave the stand when your competitor is away from the stand unless in the presenceof another expertNo use of mobile phones is permitted.Health and Safety Check ListList each item A to C'A' = Satisfactory'B' = Unsatisfactory but rectified immediately'C' = Unsatisfactory - remedial action required1.Are all exits from the area free of obstruction?2.Are all gangways within the area free from obstruction?3.Are all fire fighting appliances at their designated, location, and access to them notobstructed?4.Do Experts / Competitors in the area know:a) Means of escape in emergency.b) The location of fire equipment and alarm points.c) What action to take if the evacuation alarm sounds.d) The action to take if a person is seriously ill / injured.5.Is the floor surface safe?6.Are items of furniture in a sound condition e.g. lockers, tables, chairs, benches etc.7.Are cables and extension leads on electrical equipment, at the plug?8.Are electrical wall sockets secure and in good condition.9.Are the following satisfactory:a) Lightingb) Ventilationc) Temperatured) Noise levele) Extraction10.Are "fittings" in a safe state, e.g. lights, service supplies etc.11.Are all items of handling equipment in a safe condition, e.g. trolleys etc. and up to date.(In the area)?15Are all filing cabinet drawers functioning correctly, and are drawers prevented from coming out by limit stops.16Are metal cabinets free from sharp edges.17Are the tops of units free from unsuitable objects.18Is there suitable storage provided (and used) for cabinet drawer locking bars, when not in use.19If applicable, are paper guillotines properly guarded.20Does the area demonstrate a satisfactory level of decent house-keeping? e.g. steps, ladders etc. (are they in good condition)?22Are heavy items stored on low level racks.24Are all personnel trained to use appropriate equipment in this area (see supervision)25Are there necessary restrictions being enforced e.g. entry of unauthorised persons.26Are flammable liquids and chemicals stored in appropriate environment correctly, e.g.gloves, goggles etc?28Are the edges of areas marked with a hazard stripe.29Are all equipment that require guarding, fitted with secure are serviceable guards?30Is eye protection being worn in appropriate areas.32Are there other items of safety equipment avqilable for use.33Are tools in good condition.34Are all raw materials or equipment safely positioned.35Is there a list of authorised persons who may use machines or equipment?36Are waste materials correctly disposed of?37If chemicals or substances are used, are they in suitable containers that are correctly marked?38Is safety information for chemicals or substances used available and known to the user?39Are the emergency stop buttons on equipment assessable and clearly marked?41Are competitors supervised.42Are free standing gas bottles secured.43Are all tools in use in good condition.44Are free standing gas bottles secure.45If applicable, have all system components been subjected to test, is a certificate available?46If applicable, is equipment within validation.47If applicable, is pipe work adequately secured.48Are there written procedures for :-a) Setting up for test.b) Test procedure.c) Making safe after test.50Are the necessary restrictions being enforced e.g. entry of unauthorised personnel. 51Do all personnel know the main isolation controls of the services being used?52Are cables and flexible hoses correctly routed to prevent accidents or damage?53If flammable liquids or chemicals are being use, are they :-a) Of minimal quantity.b) In approved containers.c) Correctly labelled.54Have reasonable safety precautions been taken against any foreseeable occurrence whilst carrying out the test.55If applicable, is the equipment correctly bonded / earthed.56If competitors or others are working in the area, are they under full supervision. Chief Expert (Signature)....................................................APPENDIX 6Specifications for PCB cardsMechanical spec.’sThe Europe format for PCB card is specified as follow (PCB only):All Dimensions are in millimeters. Tc = 160 mmThe Europe format for PCB card with a front plateIs specified as follow (with front plate and DIN41612 connector):All Dimensions are in millimeters. Tc = 160 mmFront Plate dimensions (if needed): 40,64 mm x 128,7 mm x 2,5 mmPCB connectorEach card must be designed with a DIN41612 male 64 pins a + c (C form)connector for PCB. The reference from HARTING is: 0903.164.6921.Mechanical dimensions of the connector。
a rXiv:h ep-ph/3818v11Aug23∆→Nγ∗Coulomb Quadrupole Amplitude in pQCD Ahmad Idilbi,1,∗Xiangdong Ji,1,†and Jian-Ping Ma 2,‡1Department of physics,University of Maryland,College-Park,Maryland 20742,USA 2Institute of Theoretical Physics,Academia Sinica,Beijing,100080,P.R.China We present a leading-order pQCD calculation of the helicity-flip ∆→Nγ∗matrix element G 0(Coulomb quadrupole amplitude C 2),taking into account the transverse momenta of the quarks and the contribution from the gluons.In the large Q 2limit,its scaling behavior acquires a double-logarithmic correction log 2(Q 2/Λ2)compared with the standard scaling analysis,due to the contribution from the orbital motion of the small-x partons.Based on this and on the latest JLab experimental results of the C 2−M 1ratio R SM at Q 2=3∼4GeV 2,we make a phenomenological prediction for the latter at higher values of Q 2.I.INTRODUCTION In recent years,there have been continuing interests in the electromagnetic N →∆transition.One of the earlier interests was due to the work of Becchi and Morpurgo [1].In that work they had shown that in the context of the symmetric,non-relativistic,SU (6)quark model,the transition N →∆is a pure magnetic dipole M 1and the contribution from the electric quadrupole E 2is zero.One crucial assumption in their derivation of this ‘selection rule’is that the quarks in both the nucleon and the delta are in the zero orbital angular momentum states.These predictions were to be considered as a check to the validity of the quark model,which was still questionable in those ter experimental measurements [2]showed that,indeed,the magnetic dipole M 1contributes predominantly to the N →∆transition,while the contribution from E 2is small but non-vanishing.The non-vanishing value of E 2,and also the Coulomb quadrupole C 2in the case of a virtual photon,has generated much theoretical interest.One way to account for E 2=0is through the D -wave mixtures in the N and ∆wave functions [3].Another way is through the two-body electromagnetic currents from one-gluon and/or one-pion exchange between constituent quarks [4].In the latter case,it is argued that E 2transition is,mainly,due to a two-quark spin-flip operator.On the other hand,in the large N c limit of quantum chromodynamics it has been shown [5]that R EM ≡E 2/M 1is of order 1/N 2c.To derive this result,no assumption about orbital angular momentum of the quarks was necessary.More recent work in this direction can be found in Ref.[6].Another major issue related to the N →∆transition,and in general to any hadronic exclusive process,is the applicability of perturbative QCD (pQCD)at the range of values of momentum transfer Q 2accessible in the current generation of experiments.In terms of the ratios R EM and R SM≡C 2/M 1,pQCD power counting predicts that [7],in the limit Q 2→∞,R EM→1andR SM →const .,up to logarithmic corrections to be discussed in this paper.The former predictionhas not yet been observed experimentally.In fact,up to Q2=4GeV2,R EM stays negative and very close to zero[8,9,10,11,12].The comparison between data and pQCD prediction for R SM is the main topic of this paper.To make the pQCD predictions more relevant atfinite Q2where data have been and will be taken,one has to go beyond the asymptotic power counting,make detailed pQCD calculations of hard scattering amplitudes and derive the factorization formula for the experimental observables. In the present case,the relevant quantities are the three independent helicity matrix elements[7]:1Gλ=II.KINEMATICS AND NOTATIONIn this paper,we treat the bare delta as if it were a bound state of QCD,although in experiment it appears only as a resonance in certain scattering cross sections.Our analysis is relevant for scattering at the resonance peak where the contribution from the background vanishes by definition. We will not consider the so-called the dressing of the resonance due to the pion cloud which might be important at small Q2[11,12].Consider the following scattering:P(P N)+γ∗(q)→∆(P∆).(2) which appears as a sub-process of the electro-production of pions.We are interested in the G0 matrix element,in which case the photon is logitudinally-polarized and with a large virtuality Q2=−q2.Our analysis will be carried out in a frame in which the virtual photonγ∗,the incoming proton and the outgoing∆are collinear.The three momenta of the proton and the∆are in opposite directions and theγ∗is moving in the−z direction.The photon polarization vector is given by:ε(λ=0)=−1Q2(q3,0,0,q0).(3) with qµ=(q0,0,0,q3).We will also need the light-cone wave functions of the proton and the∆+(with the same charge as the proton).These wave functions are given by[15,17]:|P,λ=1/2 =112 d[1′][2′][3′]εijk ψ(1)∆(1′,2′,3′)× u†i↓(1′)u†j↓(2′)d†k↑(3′)+u†i↓(1′)d†j↓(2′)u†k↑(3′)+d†i↓(1′)u†j↓(2′)u†k↑(3′) |0+k′−2⊥ψ(3)∆(1′,2′,3′)(5)× u†i↓(1′)u†j↑(2′)d†k↑(3′)+u†i↓(1′)d†j↑(2′)u†k↑(3′)+d†i↓(1′)u†j↑(2′)u†k↑(3′) |0 +... where k±⊥=k x±ik y,the ellipses denote other components of the wave functions which do not enter the following calculation,and↑(↓)on the quark creation operators denotes the positive(negative) helicity of the quarks.The amplitudesψ(1)P,∆(ψ(3)P,∆,ψ(4)P)have zero(one)unit of the orbital angular momentum projection.ψ(1)∆(1,2,3)is symmetric in1and2.The integration measure is given by:d[1]d[2]d[3]=dx1dx2dx3x1x2x3d2k1⊥d2k2⊥d2k3⊥It should be noted that since the∆moves in−z direction then the orbital angular wave function must be k′−2⊥as shown in Eq.(5).The matrix element G0has two contributions:one in which the proton has l z=0and the∆carries l z=−1and in the second one the proton has l z=1 and the∆carries l z=0.For thefirst case,we introduce the hard amplitudes T i(1,2,3,1′,2′,3′), which represent three quark scattering offthe external photon with two-gluon exchange.The index i=1,2,3indicates that the photon is attached to i-th quark.For the second case,the hard amplitudes are denoted as T′i(1,2,3,1′,2′,3′),in which all quark helicities are reversed.We will explain how to compute these hard amplitudes in the next section.III.LEADING-ORDER PQCD F ACTORIZATION FORMULA FOR G0In this section,we derive a leading-order pQCD factorization formula for the helicity-flip Nγ∗→∆matrix element G0.As shown in Eq.(1),this is generated by a virtual photon with longitudinal polarization,corresponding to the Coulomb quadrupole amplitude.Thefirst step in calculating G0is to obtain the hard scattering amplitudes of partons.For this we follow the guidelines of Ref.[16].In principle,one has to consider both three-quark scattering with one unit of orbital angular momentum or three-quark-one-gluon scattering without orbital motion.Here we consider explicitly only the former and take into account the latter through the requirement of color gauge invariance,leaving out the contribution with the gluonfield strength tensor.This practice of leaving out dynamical gluon contribution corresponds to the so-called Wendzura-Wilczek approximation in the literature[18].A key point in the calculation is that since the quark masses are negligible,the quark helicity is conserved.This is due to the vectorial nature of the electromagnetic coupling between the struck quark and the virtual photon and of QCD quark-gluon coupling[14].When a Fock component of the light-cone wave function of the proton contains two quarks of the sameflavor and helicity then,clearly,it contributes only when there are two quarks of the sameflavor and helicity in the∆wave function.The exchange contribution that results due to the presence of the same two quarks has to be taken into account properly through the second quantized calculation.Using the light-cone wave functions of the proton and the∆in Eqs.(4)and(5)and keeping terms that are linear in the quark transverse momenta,one obtains:e u−e dG0=−(1)(2)(3)(4)(5)(6)(7)FIG.1:The leading pQCD diagrams contributing to the nucleon to∆transition amplitudes.The mirror diagrams should be added.Tofind the amplitudes T i,we let the outgoing quarks carry orbital angular momenta k′i⊥and theincoming quarks have zero orbital angular momenta,i.e.,k i⊥=0.From each one of the Feynmandiagrams we write the amplitude following the usual QED and QCD Feynman rules.Since thecalculation is performed in the collinear frame in which the particles are highly relativistic,wecan set the masses of the proton and the∆to zero.We expand the quark spinors in thefinalstate and the quark propagators tofirst order in the transverse momenta.Then we collect all suchcontributions from the given diagram and sum up the results of all the Feynman diagrams.Thisyields T i(k′i⊥,x i,y i,Q2).Tofind T′i(k i⊥,x i,y i,Q2)we set k′i⊥=0and k i⊥=0and follow similar steps.The results for T1(1,2,3,1′,2′,3′)at order of O(k⊥)are as follows:T1(1,2,3,1′,2′,3′)=−g4s8C2B¯x1¯y21x23y3+1¯y1¯x3x2y2x3y3+1¯x3y1y2y3x2x23w2(x1,x2,x3,y1,y2,y3)=1¯x21¯y1x3y23−1¯x21¯y1y3x2y2+1Similarly for T2we have:T2(1,2,3,1′,2′,3′)=−g4s8C2B¯x2¯y2x1x3y23+1¯x1x1y1x3y23+1¯x1¯y3y1x21x3y3.(11)To obtain T3(1,2,3,,1′,2′,3′)we interchange x1,y1,k′+1⊥and x3,y3,k′+3⊥and to obtain T′i(1,2,3,1′,2′,3′)we replace k′+i⊥with k+i⊥and interchange x i and y i.The above results are consistent with those derived in Ref.[16].To further simplify the above expressions,let us define k⊥-intergrated wave functions:φ(3)P(x1,x2,x3)=2 [d2k⊥]ψ(1)P(k1,k2,k3)φ(4)P(x1,x2,x3)=2 [d2k⊥]k3⊥·(k2⊥ψ(3)P+k1⊥ψ(4)P)(k2,k1,k3),ψ(4)P(x1,x2,x3)=2 [d2k⊥]k1⊥·(k2⊥ψ(3)P+k1⊥ψ(4)P)(k2,k1,k3)φ(3)∆(x1,x2,x3)=2 [d2k⊥]ψ(1)∆(k1,k2,k3)φ(4)∆(x1,x2,x3)=2 [d2k⊥]k3⊥·k1⊥ψ(3)∆(k2,k1,k3),ψ(4)∆(x1,x2,x3)=2 [d2k⊥]k1⊥·k1⊥ψ(3)∆(k2,k1,k3)(12) where the integration measure is defined as:[d2k⊥]=d2k1⊥d2k2⊥d2k3⊥(2M N)4Q4e u−e dwhere[dx]=dx1dx2dx3δ(1−x1−x2−x3)andαs=g2s/4π.We see from Eq.(13)that G0scales like 1/Q4in the high Q2limit,consistent with the general power counting.Tofind the normalization of G0we need to know the light-cone distribution amplitudes defined in Eq.(12).For the proton, a set of such functions have been given in Ref.[19]based on conformal expansion,QCD sum rules and Lorentz symmetry.For the∆no such work has been done explicitly.However if the∆is to be treated as a three-quark state,we believe that,at the asymptotically large Q2,the light-cone distribution amplitudes of the∆will have a y i-dependence which is identical to the x i-dependence of the light-cone distribution amplitudes of the proton[20].For the proton we have,for example, the asymptotic form ofφ(3)p is x1x2x3andφ(4)p is x1x2[13].If we perform the x i and y i integration in Eq.(13)with such functions we get,due to end-point singularities,a double logarithmic divergence results.This divergence indicates the quarks with small Feynman x contribute significantly to the hard scattering.However,for very small x for which the parton longitudinal momentum is on the order ofΛQCD,the hard scattering picture breaks down,and the above calculation is invalid.Then one has to add the so-called Feynman contribution which is relatively unimportant in the limit of large Q2.Therefore,these divergent integrals are regulated physically by a cut-offfrom below of order Λ2/Q2whereΛis some parameter that represents the soft energy scale(order of few hundreds of MeV).With this cut-off,the result of the momentum fraction integration will be a Q2-dependent term of the form,log2(Q2/Λ2).Thus we can write:G0=c′log2(Q2/Λ2)/Q4(14) where c′is a numerical factor that depends on the explicit expressions of the light-cone distribution amplitudes.With this form of G0and with the fact that G−is of order1/Q2relative to G+we will give in the next section a phenomenological prediction of the ratio R SM in the high Q2limit.IV.PHENOMENOLOGYIn the electro-production of the∆resonance,the multipoles M1,E2and C2of the exchanged virtual photon are the only ones that contribute[21,22,23,24].One of the experimentally extracted quantities related to this process is the ratio R SM≡C2/M1.In order to express this ratio in terms of the helicity matrix elements Gλwe introduce the resonance“helicity amplitudes”A1/2,A3/2and S1/2[25].These amplitudes are computed in the rest frame of the∆and the sub-indices refer to the helicity of the∆.The scalar amplitude S1/2is relevant only for virtual photons.These amplitudes are related to the helicity matrix elements through the relations[26]:A1/2=ηG+;A3/2=ηG−;S1/2=η|q|M2∆+M2N+Q22A1/2−√2A3/2(16) 7-0.3-0.2-0.10.12468101214R S M Q 2 (GeV 2)FIG.2:A phenomenological prediction for the ratio R SM .From the results of the previous section we see that A 3/2is of order 1/Q 2relative to A 1/2in the high Q 2limit and thus it will be neglected.With this approximation the ratio R SM becomes:R SM =|q |G +(17)Substituting in the last equation the expression for |q |and using Eq.(14)we get:R SM =c 2.464 2−.88log 2(Q 2/Λ2)−.88+(2.4+Q 2)2log 2(16Q 2)V.SUMMARYA perturbative QCD calculation of the helicityflip matrix element of the electromagneticN→∆transition has been given.We showed that the transverse momenta of the quarks inthe proton and∆is essential to obtain afinite result.An explicit calculation of the hard ampli-tude T i(x i,y i,k′i⊥,Q2)and T′i(x i,y i,k i⊥,Q2)has been given and the techniques of the calculationwere outlined in some detail.The essential steps of the calculation are to draw the relevant per-turbative Feynman diagrams and then to compute the contribution from each such diagram byexpanding the quark spinors and propagators tofirst power of the transverse momenta.The hardamplitudes are then to be convoluted with light-cone amplitudes.Our pQCD results for the scalingbehavior of G+,G0and G−confirm earlier scaling prediction[7].In addition we outlined how oneobtains the double logarithmic correction.Based on our result for Gλwe gave a phenomenologicalprediction for the ratio R SM.Roughly speaking,|R SM|will be of order of20%at Q2of order10 GeV2.We thank A.V.Belitsky,C.Carlson,P.Stoler,and F.Yuan for a number of useful discussions.[1] C.Becchi,G.Morpurgo,Phys.Lett.17(1965)352.[2]R.H.Dalitz,D.G.Sutherland,Phys.Rev.146(1966)1180.[3]S.S.Gershtein,G.V.Dzhikiya,Sov.J.Nucl.Phys.34(1982)870;N.Isgur,G.Karl,R.Koniuk,Phys.Rev.D25(1982)2394.[4] A.J.Buchmann,E.Hern´a ndez,A.Faessler,Phys.Rev.C55(1977)448;A.J.Buchmann,E.Hern´a ndez,K.Yazaki,Phys.Lett.B269(1991)35;Nucl.Phys.A569(1994)661.[5] E.Jenkins,X.Ji,A.Manohar,Phys.Rev.Lett.89(2002)242001.[6] A.J.Buchmann,J.A Hester,R.F Lebed,Phys.Rev.D66(2002)056002.[7] C.E.Carlson,Phys.Rev.D34(1986)2704.[8]R.Beck et al.,Phys.Rev.Lett.78(1997)606.[9] F.Kalleicher et al.,Z.Phys.A359(1997)201.[10]V.V.Frolov et al.,Phys.Rev.Lett.82(1999)45.[11]S.S.Kamalov,Shin Nan Yang,Phys.Rev.Lett.83(1999)4494.[12]T.Sato,T.S.H.Lee,Phys.Rev.C54(1996)2660.[13]S.J.Brodsky,G.P.Lepage,Phys.Rev.Lett.43(1979)545.[14]G.P.Lepage,S.J.Brodsky,Phys.Rev.D22(1980)2157.[15]X.Ji,J.-P.Ma,F.Yuan,Phys.Rev.Lett.90(2003)241601.[16] A.V.Belitsky,X.Ji,F.Yuan,hep-ph/0212351,to appear in Phys.Rev.Lett.[17]X.Ji,J.-P.Ma,F.Yuan,hep-ph/0304107.[18]S.Wendzura,F.Wilczek,Phys.Lett.72(1977)195.[19]V.M.Braun,R.J.Fries,N.Mahnke,E.Stein,Nucl.Phys.B589(2000)381.[20] A.Idilbi,X.Ji,and J.-P.Ma,to be published.[21]H.F.Jones,M.D.Scadron,Ann.Phys.(N.Y)81(1973)1.[22]L.Durand,P.C.DeCelles,R.B.Marr,Phys.Rev.126(1962)1882.[23] A.J.Dufner,Y.S.Tsai,Phys.Rev.168(1968)1801.[24]R.C.E.Devenish,T.S.Eisenschitz,J.G.K¨o rner,Phys.Rev.D14(1976)3063.[25]L.A.Copley,G.Karl,E.Obryk,Phys.Lett.B299(1969)117;Nucl.Phys.B13(1969)303.[26]P.Stoler,Phys.Rep.226(1993)103.[27]R.M.Davidson,Nimai C.Mukhopadhyay,R.S.Wittman,Phys.Rev.D43(1991)71.9。
Respiratory Drug Delivery 2014 – Cooper et al.A QbD Method DevelopmentApproach for the Ex-actuatorParticle Size Distribution (PSD)Determination of pMDIsby Laser DiffractionAndy Cooper,1 Chris Blatchford,1and Stephen Stein213M Drug Delivery Systems Ltd, Loughborough,Leicestershire,UK23M Drug Delivery Systems, St. Paul, MN, USAKEYWORDS: pressurized metered dose inhaler (pMDI),quality by design (QbD), laser diffraction,method development, particle sizeIntRODuCtIOnThe aerodynamic particle size distribution (APSD) is a critical quality attribute (CQA) of orally inhaled and nasal drug products (OINDPs). Cascade impactor methodology [1] is typically used to determine this during development and registered product testing. However, this is a time consuming analysis which makes it impractical as a rapid screening tool for early phase develop-ment and investigations. Laser diffraction (LD) analysis of the ex-actuator plume has previously been proposed as an alternative [2] for geometric particle size distribution (PSD) determination. This is considered appropriate as the measured ex-actuator PSD would be influenced by the active pharmaceutical ingredient (API) within the formulation in three ways. One, the dry API par-ticles would be present in the actuation plume after atomization. Two, droplet formation during atomization may be influenced by the particle size of the API [3]. Lastly, the API concentration will influence the number of particles within each droplet and hence the measured PSD [2, 4]. This publication will focus on the specific considerations for method development/validation of this methodology [5-11], using a quality by design (QbD) approach [11, 12]. Data from these methods have the potential to correlate with APSD data [3, 14], as many variables are common to both techniques [15], despite the difference in the principle of measurement (geometric versus aerodynamic).321322QbD Method Development for the Ex-actuator PSD of pMDIs by Laser Diffraction – Cooper et al.MEthODOLOgYMeasurements were made with a Sympatec™ instrument, consisting of a Helos (Helium-Neon Laser Optical System)/BF™ laser diffraction sensor with the Inhaler™ dry dispersion accessory (See instrument settings in Table 1). The pMDI unit is manually actuated into the Inhaler accessory, allowing the actuation plume to pass through the laser (He/Ne @ 633nm) where light is scattered and then focused by a chosen lens onto a detector array. The detector consists of 31 concentric ring elements. The innermost element is referred to as R1 and the outermost element as R31. Scattered light registered on elements R1-R6 is discounted due to beam steer [16]. The signals from all the other detector elements are combined and a PSD is inferred from the scattering pattern based on the chosen optical model, after subtraction of background levels.table 1.Sympatec™ instrument settings.RESuL tS AnD DISCuSSIOnThere are multiple variables which can influence laser diffraction data, as shown in Figure 1. Aside from the product related factors, risk assessments of the other variables are required. While some parameters have no impact if they are suitably controlled (e.g., cleaning), other more critical parameters require experimenta-tion to determine their effects (e.g., trigger conditions). The Inhaler accessory was chosen since the droplets are entrained in an air flow which dilutes the sample and reduces potential artefacts such as velocity bias and geometric effects [15].Figure 1. Fishbone diagram of sources of variability for laser diffraction data.Respiratory Drug Delivery 2014 – Cooper et al. 323Copyright © 2014 VCUThe length of cylinder used for the Inhaler accessory must be optimized. This dictates thedistance between the point of actuation and the laser beam. The optical concentration (OC) must be sufficient for sensitivity purposes but not too high to cause multiple scattering. Data are shown in Figure 2A and 2B. The similarity in OC for the active and placebo shows that the majority of light did not reach the central detector due to the propellant shifting the laser beam (beam steer). The median particle size for the placebo is decreased with increased distance. This is likely due to the increased evaporation of co-solvent, rather than an indication of multiple scattering. This signal observed for the placebo led to the refractive index of the co-solvent being chosen for the method. Although the OC decreased with increased firing distance due to reduced beam steer, the active PSD remains reasonably consistent [<10% shift in d(v, 0.5)] and is considered to be real. A slight increase in active median particle size is consistent with reduced interference from the co-solvent and therefore the long cylinder is considered to be the most accurate.Figure 2. A: Optical concentration. B: d(v, 0.5) data for high strength active and placebo for various cylinder lengths.The selection of sampling criteria (trigger conditions) is critical [4] and they can alsointeract with the method of shaking and firing, particularly for a suspension pMDI. Design experi-ments are crucial for method optimization and for proving method robustness. Parameters, which are selected via a suitable risk assessment, are evaluated over an appropriate design space, as shownin Figure 3.324QbD Method Development for the Ex-actuator PSD of pMDIs by Laser Diffraction – Cooper et al.Figure 3. PSD data for sample preparation DoE – low strength active.Validation data for this method are shown in Table 2. Validation was performed on both high and low strength actives. RSD values are higher than those typically observed for a laser diffraction method for an API [17], however this is likely due to the inherent product variability (See Figure 1) – measurements are made of volatile droplets with a wide range of velocities contributing to differing amounts of evaporation per droplet. Increased variability is therefore expected. However, one important factor to limit variability is humidity level [4].table 2.Method validation data.This validated method has been used to try and understand trends in APSD data. The data shown in Table 3 shows that the PSD is influenced by the temperature of the product, which has similar trends to those observed for ACI data in the literature [18]. The vapor pressure of the formulation increases with temperature, which results in atomization of smaller droplets, which will contain fewer drug particles, hence a decrease in PSD. Faster propellant/co-solvent evaporation, due to the increased temperature, will also result in a decrease in PSD.table 3.PSD data for a range of temperatures (n = 6 at each condition) – high strength active.Respiratory Drug Delivery 2014 – Cooper et al. 325COnCLuSIOnSA QbD approach to development of laser diffraction (LD) methodology to determine the PSD ex-actuator from a pressurized metered dose inhaler (pMDI) is presented. Robust and repeatable data were obtained, however this is inherently more variable than methodology for the PSD deter-mination of the API. The LD methodology can be used to understand trends in cascade impaction data – the industry standard, but more time consuming, methodology for APSD determination.REFEREnCES1. USP Chapter (601): Aerosols, nasal sprays, metered-dose inhalers, and dry powder inhalers.2. Gonda, I: Development of a systematic theory of suspension inhalation aerosols. A frameworkto study the effects of aggregation on the aerodynamic behaviour of drug particles, International Journal of Pharmaceutics 1985, 27: 99-116.3. Pu, Y, Kline, LC, Berry, J: The application of “in-flight” laser diffraction to the particle sizecharacterization of a model suspension metered dose inhaler, Drug Development and Industrial Pharmacy 2011, 37 (5): 552-58.4. Cooper, A, Bell, T: Monitoring of droplet size changes in a suspension pMDI by laserdiffraction on a Sympatec™Instrument. In Drug Delivery to the Lungs 19, 2008.5. Mitchell, JP, Nagel, MW, Nichols, S, Nerbrink, O: Laser diffractometry as a technique for therapid assessment of aerosol particle size from inhalers, Journal of Aerosol Medicine 2006, 19(4): 409-33.6. ICH Harmonised Tripartite Guideline Q2(R1) (1994): Validation of analytical procedures,Text and Methodology.7. ISO Standard 13320-1 (2009): Particle size analysis, laser diffraction methods.8. Ph. Eur. Chapter 2.9.31: Particle size analysis by laser light diffraction.9. USP Chapter (429): Light diffraction measurement of particle size.10. Ward-Smith, RS, Gummery, N, Rawle, AF: Validation of wet and dry laser diffraction particlecharacterisation methods. Malvern Instruments Ltd. /malvern/kbase.nsf/allbyno/KB000167/$file/Laser%20Diffraction%20Method%20Validation.pdf.11. Rawle, A, Kippax, P: Setting new standards for laser diffraction particle size analysis. MalvernInstruments Ltd. /malvern/kbase.nsf/allbyno/KB002403/$file MRK 1399-01.pdf.Copyright © 2014 VCU326QbD Method Development for the Ex-actuator PSD of pMDIs by Laser Diffraction – Cooper et al.12. Schweitzer, M, Pohl, M, Hanna-Brown, M, Nethercote, P, Borman, P, Hansen, G, Smith,K, Wegener, G: I mplications and opportunities of applying QbD principles to analytical measurements, Pharmaceutical Technology 2010, 34 (2): 52-59.13. Borman, P, Chatfield, M, Jackson, P, Laures, A, Okafo, G: Reduced-method robustness testingof analytical methods driven by a risk-based approach, Pharmaceutical Technology 2010, 34(4): 72-86.14. Jones, SA, Martin, GP, Brown, M.B: High-pressure aerosol suspensions – A novel laserdiffraction particle sizing system for hydrofluoroalkane pressurised metered dose inhalers, International Journal of Pharmaceutics 2005, 302: 154-65.15. Blatchford, C: From powder to patient - optimisation of particle sizing techniques, In DrugDelivery to the Lungs 24, 2013.16. Ranucci, J: Dynamic plume – particle size analysis using laser diffraction, PharmaceuticalTechnology 1992, 16: 108-14.17. Cooper, A, Blatchford, C, Kelly, M: Laser diffraction methodology for particle size distribution(PSD) determination during pMDI product development – A QbD approach. In Respiratory Drug Delivery Europe 2013. Volume 2. Edited by Dalby, RN, Byron, PR, Peart, J, Suman, JD, Young, PM, Traini, D. DHI Publishing; River Grove, IL: 2013: 197-202.18. Stein, S, Cocks, P: Size distribution measurements from metered dose inhalers at lowtemperatures. I n Respiratory Drug Delivery Europe 2013. Volume 2. Edited by Dalby, RN, Byron, PR, Peart, J, Suman, JD, Young, PM, Traini, D. DHI Publishing; River Grove, IL: 2013: 203-08.。
201507FDA行业指南：分析方法验证（中英文）（中）A. Principle/Scope 原理/范围A description of the basic principles of the analytical test/technology (i.e., separation, detection); target analyte(s) and sample(s) type (e.g., drug substance, drug product, impurities or compounds in biological fluids).分析测试/技术（即分离、检测）基本原因的描述；目标分析物和样品类型（例如，原料药、制剂、杂质或生物流体中的化合物）。
B. Apparatus/Equipment 仪器/设备All required qualified equipment and components (e.g., instrument type, detector, column type, dimensions, and alternative column, filter type).所有需要的确认过的仪器和组件（例如，仪器类型、检测器、柱子类型、尺寸和可替代的柱子、过滤器类型）。
C. Operating Parameters 运行参数Qualified optimal settings and ranges (include allowed adjustments supported by compendial sources or development and/or validation studies) critical to the analysis (e.g., flow rate, components temperatures, run time, detector settings, gradient, head space sampler). A drawing with experimental configuration and integration parameters may be used, as applicable.确认过的优化的设置和范围（包括来自药典或研发和/或验证研究的允许调整），对于分析过程非常关键（例如，流速、部件温度、运行时间、检测器设置、梯度、顶空进样器）。
pqmp 量化管理计划A pqmp (quantitative management plan) is a crucial tool in project management that aims to ensure effective and efficient execution of a project. It involves the use of quantitative techniques and metrics to monitor and control various aspects of a project, such as cost, schedule, quality, and risk. By establishing clear objectives,defining performance measures, and implementing appropriate monitoring and control mechanisms, a pqmp helps project managers make informed decisions, identify potential issues, and take corrective actions to keep the project on track.One of the key benefits of a pqmp is its ability to provide a structured approach to project management. By establishing clear objectives and performance measures, it helps project managers and teams focus on what needs to be achieved and how success will be measured. This clarity of purpose and direction enhances team coordination, reduces ambiguity, and improves overall project outcomes. Moreover, a pqmp helps in setting realistic goals, allocatingresources effectively, and managing stakeholder expectations, leading to increased project success rates.Another advantage of a pqmp is its ability tofacilitate data-driven decision-making. By utilizing quantitative techniques and metrics, project managers can gather and analyze relevant data to gain insights into project performance. This enables them to identify trends, patterns, and potential risks, allowing for timely interventions and corrective actions. For instance, if the cost of a project is exceeding the budget, a pqmp can help identify the specific cost drivers and suggest appropriate cost-cutting measures. Similarly, if the project is falling behind schedule, a pqmp can highlight the criticalactivities and help in reallocating resources or adjusting the project plan accordingly.Furthermore, a pqmp promotes accountability and transparency in project management. By defining clear performance measures and monitoring mechanisms, it ensures that project progress is regularly tracked and reported. This not only helps project managers stay informed aboutthe project's status but also enables effective communication with stakeholders. By providing accurate and timely information, a pqmp fosters trust, reduces conflicts, and enhances collaboration among project team members and stakeholders.In addition to these benefits, a pqmp also plays a crucial role in risk management. By incorporating risk assessment and mitigation strategies, it helps project managers identify and address potential risks proactively. This includes analyzing the probability and impact of risks, developing contingency plans, and monitoring riskindicators throughout the project lifecycle. By doing so, a pqmp minimizes the likelihood of project failures, enhances resilience, and improves overall project outcomes.However, it is important to note that a pqmp is not a one-size-fits-all solution. It should be tailored to the specific needs and characteristics of each project. This requires a thorough understanding of the project's objectives, constraints, and stakeholders. Additionally,the success of a pqmp relies heavily on the availability ofaccurate and reliable data. Therefore, project managers must ensure that appropriate data collection and analysis mechanisms are in place to support the implementation of a pqmp.In conclusion, a pqmp is an essential tool in project management that enables effective planning, monitoring, and control of projects. By utilizing quantitative techniques and metrics, it provides a structured approach to project management, facilitates data-driven decision-making, promotes accountability and transparency, and enhances risk management. However, it is important to customize a pqmp to the specific needs of each project and ensure the availability of accurate data. Ultimately, a well-implemented pqmp can significantly improve project outcomes and increase the likelihood of success.。
a rXiv:h ep-ph/21198v114Oct22PQCD approach to exclusive B decays 1Hsiang-nan Li Institute of Physics,Academia Sinica,Taipei,Taiwan 115,Republic of China Abstract I review the recent progress on the perturbative QCD approach to exclu-sive B meson decays,discussing the comparison of collinear and k T factoriza-tions,the CP asymmetry in the B 0→π+π−decay,penguin enhancement,the branching ratio of the B 0→D 0π0decay,and three-body nonleptonic decays.1Introduction Both collinear and k T factorizations are the fundamental tools of perturbative QCD (PQCD),where k T denotes parton transverse momenta.For inclusive processes,such as deeply inelastic scattering (DIS)of a hadron,collinear (k T )factorization applies when the process is measured at a large (small)Bjorken variable x B [1]([2,3,4]).For exclusive processes,collinear factorization was developed in [5,6,7,8],in which a physical quantity is written as the convolution of a hard amplitude with hadron distribution amplitudes in parton momentum fractions x .In the inclusive case the range of a momentum fraction x ≥x B is experimentally controllable.In the exclusive case the range of a momentum fraction is not controllable,and must be integrated overbetween 0and 1.Hence,one must deal with the end-point region with a small x .If a hard amplitude does not develop an end-point singularity,collinear factorization works.If such a singularity occurs,collinear factorization breaks down,and k T factorization [9,10]should be employed.Based on the concepts of collinear and k T factorizations,the PQCD [11]and QCD factorization (QCDF)[12]approaches to exclusive B meson decays have been developed,respectively.The soft-collinear effective theory is a sys-tematic framework for the study of collinear factorization[13].As applyingcollinear factorization to the semileptonic decay B→πℓ¯νat large recoil, an end-point singularity from x→0was observed[14].According to theabove explanation,we conclude that exclusive B meson decays demand k Tfactorization[15,16,17].As shown in[18],predictions for exclusive processes derived from k T factorization are gauge-invariant.In the PQCD approachthe B→h1h2decay amplitude is written as the convolution[19,20,21,22],A=φB⊗H(6)⊗φh1⊗φh2⊗S,(1) where the six-quark amplitude H(6)corresponds to the diagrams with a hard gluon emitted from the spectator quark[23],and S denotes the Sudakovfactor.Once parton transverse momenta k T are included[15],the end-point sin-gularities from small momentum fractions in exclusive B meson decays aresmeared.The resummation of the resultant double logarithmsαs ln2(P b), where P denotes the dominant light-cone component of a meson momen-tum,and b is the variable conjugate to k T,leads to a Sudakov form factor exp[−s(P,b)].This factor suppresses the long-distance contributions fromthe large b region with b∼1/¯Λ,where¯Λ≡M B−m b,M B(m b)being the B meson(b quark)mass,represents a soft scale.The suppression renders k2Tflowing into the hard amplitudes of O(¯ΛM B).The off-shellness of in-ternal particles then remain of O(¯ΛM B)even in the end-point region,andthe singularities are removed.Since the end-point singularities do not exist [15,24,25,26],the arbitrary cutoffs introduced in QCDF[12,27]are not nec-essary.Therefore,factorizable,nonfactorizable and annihilation amplitudes can be estimated in a more consistent way in PQCD than in QCDF.2CP AsymmetriesPhenomenological consequences for two-body nonleptonic B meson decays derived from collinear and k T factorizations are quite different.Here we mention only the predictions for the CP asymmetry in the B0d→π+π−decay. According to the QCDF power counting rules[12,27]based on collinear factorization,the factorizable emission diagram gives the leading contribution of O(α0s),since the B→πform factor is not calculable.Because the leading contribution is real,the strong phase arises from the factorizable annihilation diagram,being of O(αs m0/M B),and from the vertex correction to the leading2diagram,being of O(αs).For m0/M B slightly smaller than unity,the vertexcorrection is the leading source of strong phases.In k T factorization the power counting rules change[28].The factorizable emission diagram is calculableand of O(αs).The factorizable annihilation diagram has the same powercounting as in QCDF.The vertex correction becomes of O(α2s).Therefore, the annihilation diagram contributes the leading strong phase.This is thereason the strong phases derived from PQCD and from QCDF are opposite in sign,and the former has a large magnitude.The detailed reason is referredto[28].As a consequence of the different power counting rules,QCDF prefersa small and positive CP asymmetry Cππ[29],while PQCD prefers a large and negative Cππ∼−30%[30,31,32,33,34].In the near future the two approaches to exclusive B meson decays,collinear and k T factorizations, could be distinguished by experiments[35,36].Significant CP asymmetries are also expected in the B→Kπ[11],B→KK[37]and B→ρK,ωK[38]decays.The last two modes are especially sensititve to the annihilation contributions.It has been pointed out[39]that contribution from intrinsic charms,one of the higher B meson Fock states, reduces the magnitude but does notflip the sign of the CP asymmetries in the B→Kπdecays.It implies that PQCD has caught the correct leading picture of exclusive B meson decays.3Penguin EnhancementThe leading factorizable contributions involve four-quark hard amplitudes in QCDF,but six-quark hard amplitudes in PQCD.This distinction also implies different characteristic scales in the two approaches:the former is characterized by m b,while the latter is characterized by the virtuality of internal particles of ordernate,such that their branching ratios are insensitive to the variation of theunitarity angleφ3.Because theφmeson is a vector meson,the mass m0is replaced by the physical mass Mφ∼1GeV,and the chiral enhancement does not exist.If the branching ratios of the B→φK decays are around4×10−6[42,43],the chiral enhancement may be essential for the penguin-dominated decay modes.If the branching ratios are around10×10−6as predicted in PQCD[28,44],the dynamical enhancement may be essential.However,it should be mentioned that the infrared cutoffs in QCDF have been assumed to be different in the B→P P and V P decay amplitudes[45].Introducing two independent sets of free parameters for the B→P P and V P modes, the B→φK branching ratios can befit without increasing the B→Kπbranching ratios.Nevertheless,the B→φK branching ratios are enhanced by large annihilation contributions[45],which seem to violate the QCDF power counting rules.4B→D0π0The PQCD formalism for B→D(∗)transitions has been developed[46], which holds under the hierachy,M B≫M D(∗)≫¯Λ,(2) with M D(∗)being the D(∗)meson mass.The relation M B≫M D(∗)justifies perturbative evaluation of the B→D(∗)form factors at large recoil and the definition of light-cone D(∗)meson wave functions.The relation M D(∗)≫¯Λjustifies the power expansion in the parameter¯Λ/M D(∗).We have calcu-lated the B→D(∗)form factors as double expansions in M D(∗)/M B and in¯Λ/MD(∗),and found that the leading PQCD factorization formulas respectthe heavy-quark symmetry.Based on the power counting rules constructed in[46],it can be shown that the relative importance of the different topologies of diagrams for the B→Dπdecays is given byemission:nonfactorizable=1:M Dto the parameters a1and a2in PQCD,respectively,the ratio|a2|/a1∼0.5is obtained.Moreover,the imaginary nonfactorizable amplitudes determine the relative phase of the factorizable and nonfactorizable contributions,which is about−57o.The PQCD predictions for the B→Dπbranching ratios[47],B(B−→D0π−)∼5.5×10−3,B(¯B0→D+π−)∼2.8×10−3,B(¯B0→D0π0)∼2.6×10−4,(4) are consistent with the experimental data,including those recently observed for the¯B d→D(∗)0π0decay[48,49,50].Hence,we are not convinced by the conclusion drawn from the factorization assumption that the B→D0π0 data hint largefinal-state interaction[51,52,53,54](see also[55]).5Three-body DecaysThree-body nonleptonic B meson decays have been observed recently[56,57]. Viewing the experimental progress,it is urgent to construct a reliable frame-work for these modes.Motivated by its theoretical self-consistency and phe-nomenological success,we have generalized PQCD to three-body nonleptonic B meson decays[58].A direct evaluation of the hard amplitudes,which con-tain two virtual gluons at lowest order,is,on one hand,not practical due to the enormous number of diagrams.On the other hand,the region with the two gluons being hard simultaneously is power-suppressed and not im-portant.Therefore,a new input is necessary in order to catch dominant contributions to three-body decays in a simple manner.The idea is to intro-duce two-meson distribution amplitudes[59],by means of which the anal-ysis is simplified into the one for two-body decays(number of diagrams is greatly reduced).Both nonresonant contributions and resonant contribu-tions through two-body channels can be included.Moreover,the application of this formalism to three-body baryonic decays[60]is straightforward.Here we pick up the leading term in the complete Gegenbauer expansion of the two-pion distribution amplitudesΦ(z,ζ,w2)[59]:Φv(z,ζ,w2)=3Fπ(w2)2N cz(1−z)(2ζ−1),Φs,t(z,ζ,w2)=3F s,t(w2)2N cz(1−z),(5) 5where the subscripts v,s and t stand for the vector,scalar and tensor com-ponents,respectively.The variable z(ζ)is the parton(pion)momentum fraction,and Fπ,s,t(w2)the time-like pion electromagnetic,scalar and tensor form factors with Fπ,s,t(0)=1.That is,the two-pion distribution amplitudes are normalized to the time-like form factors.To calculate the nonresonant contribution,we propose the parametriza-tion,F(nr)π(w2)=m2w3+m0m2,(6)where the the parameter m=1GeV is determined by thefit to the exper-imental data M2J/ψ|Fπ(M2J/ψ)|2∼0.9GeV2[61],M J/ψbeing the J/ψmeson mass.To calculate the resonant contribution,we parametrize it into the time-like form factors,F(r)π,s,t(w2)=M2V(w2−M2V)2+Γ2V w2−M2V6ConclusionI have briefly reviewed the PQCD approach to two-body nonleptonic B meson decays.This approach is based on the rigorous k T factorization theorem,in which both meson wave functions and hard amplitudes can be constructed in a gauge-invariant way.The predictions for the branching ratios and the CP asymmetries of varous modes are in agreement with the experimental data[34].The B→Kη′data are an exception,which may indicate a significant gluon content of theη′meson[64,65,66].The charm penguin contribution could be significant,and requires more investigation[67,68]. The generalization to three-body nonleptonic decays seem to be successful. In the future we shall work out the next-to-leading-order and next-to-leading-power corrections,which are expected to be more essentail for the B→ππdecays.I thank members in the PQCD working group for useful discussions.The work was supported in part by the National Science Council of R.O.C.under the Grant No.NSC-91-2112-M-001-053,by the National Center for Theoret-ical Science of R.O.C.,and by Theory Group of KEK,Japan. 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