guide to drug development a comprehensive review and assessment
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guide to drug development a comprehensive review and assessmentPlease ob- Failure to Pay special attention to the messages high- components must be performed only by lighted by these signal words.Please ob- serve all WARNINGS, CAUTIONS and WARNING: “Service Precautions” under “On-Vehicle Indicates a potential hazard that could result Service”. When replacing parts or servicing by disassembling, it is recommended to use SUZUKI genuine parts, tools and service materials (lubricant, sealants, etc.) as specified in each description. Also, there is a TABLE OF CONTENTS on the first page of EACH SECTION, where the main items in that section are listed. Driver and Passenger Air Bag (Inflator) Modules D For handling and storage of a live air bag (inflator) module, select a place where the ambient temperature. Never strike or jar the SDM. D Never power up the air bag system when the SDM is not rigidly attached to the vehicle. All SDM and mount- ing bracket fasteners must be carefully torqued and the arrow must be pointing toward the front of the ve- hicle to ensure proper operation of the air bag system. These general precautions apply to many of the service procedures described in this manual, and they will not necessarily be repeated with each procedure to which they apply. WARNING: D Whenever raising a vehicle for service, be sure to follow the instructions under “VEHICLE LIFTING POINTS”. When reconnect- ing the battery, connect the positive cable first and then the negative cable, and replace the terminal cover. D When removing parts that are to be reused, be sure to keep them arranged in an orderly manner so that they may be re- installed in the proper order and position. D After servicing fuel, oil, coolant, vacuum, exhaust or brake systems, check all lines related to the system for leaks. D For vehicles equipped with fuel injection systems, never disconnect the fuel line between the fuel pump and injector without first releasing the fuel pressure, or fuel can be.http://www.1smart.nu/images/custom/file/fleck-econominder-manual.xml
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PRECAUTION FOR CATALYTIC CONVERTER For vehicles equipped with a catalytic converter, use only un- leaded gasoline and be careful not to let a large amount of un- burned gasoline enter the converter or it can be damaged. D Be careful not to touch the electrical terminals of parts which use microcomputers (e.g. electronic control unit like as ECM, TCM, ABS control module, SDM etc). D Before measuring voltage at each terminal, check to make sure that battery voltage is 11V or higher. Such terminal voltage check at low battery voltage will lead to erroneous diagnosis. Failure to follow cautions may adversely affect electronic con- trol system. D Keep the antenna as far away as possible from the vehicle’s electronic control unit. Otherwise, rear wheels are driven and vehicle accidents, damage and personal injury may result. When a check for proper connection is requested in a diag- nostic flow chart, perform careful check of suspect circuits for: D Poor mating of connector halves, or terminals not fully seated in the connector body (backed out). D Before lifting up the vehicle, check to be sure that end of hoist arm is not in contact with brake pipe, fuel pipe, bracket or any other part. One is single-colored wire and the other is dual-colored (striped) wire. When replacing any fasteners, it is most important that replace- ment fasteners be the correct diameter, thread pitch and strength. FASTENER STRENGTH IDENTIFICATION Most commonly used metric fastener strength property classes are 4T, 6.8, 7T, 8.8 and radial line with the class identification em- bossed on the head of each bolt. If no description or specifi- cation is provided, refer to the following tightening torque chart for the applicable torque for each fastener. When a fastener of greater strength than the original one is used, however, use the torque specified for the original fasten- NOTE: D For the flanged bolt, flanged nut and self-lock nut of 4T and 7T strength, add 10 to the tightening torque.http://www.kitchensandinteriors.com.au/images/uploadedimages/fleck-econominder-5600-manual.xml Refer to “Air Bag System Components and Wiring Location View” un- der “General Description” in air bag system section in order to confirm whether you are perform- ing service on or near the air bag system components or wiring. Beyond 90,000 km (54,000 miles), carry out the same services at Interval: the same intervals respectively. This interval should be judged by This interval should be judged by ( 1,000) odometer reading or months,. Beyond 90,000 km (54,000 miles), carry out the same services at Interval: the same intervals respectively. This interval should be judged by This interval should be judged by ( 1,000) odometer reading or months, whichever comes first. Refer to SECTION 6B for replacement procedure of pump belt.Refer to SECTION 6A1 for valve lash inspection and adjust- ment procedure. When cold (Cool- When hot (Cool- ant temperature. CAUTION: To tighten oil filter properly, it is important to accurate- ly identify the position at which filter O-ring first con- tacts mounting surface. Scald- ing fluid and steam can be blown out under pressure if cap is taken off too soon. D Check exhaust system for leakage, loose connections, dents, and damages. If bolts or nuts are loose, tighten them to specification. Make sure all clamps are secure. D Replace any damaged or deteriorate parts. There should be no sign of fuel leakage or moisture at any fuel connection. Drain existing fluid from brake system completely, fill system with specified fluid and carry out air purge operation. For air purging procedure, refer to SECTION 5. ITEM 5-4 “a”: Parking brake lever stroke: Brake Lever and Cable Inspection. If defec- tive, replace. 1. Wear indicator 2) Check inflating pressure of each tire and adjust pressure to specification as necessary. If loose- ness is found, tighten to specified torque. 2) Check propeller shaft joints for wear, play and damage. If any defect is found, replace. Repair or replace defective parts, if any.http://www.familyreunionapp.com/family/events/dimplex-ofc-2009-manual 3) Check boots of steering linkage and steering gear case for dam- age (leaks, detachment, tear, etc.). If damage is found, replace defective boot with new one. Repair leaky point, if any. 2) Make sure that the vehicle is placed level for oil level check. 3) Remove level plug of differential. For replacement procedure, refer to ON-VEHICLE SERVICE in SECTION 7B or 7B1. 1. Radiator 2. Inlet hose (Outlet from oil cooler) 3. The starter should crank only in “P” WARNING: (Park) or “N” (Neutral). When carrying out road tests, select a safe On manual transmission vehicles, place the shift lever place where no man or no running vehicle is in “Neutral,”. Check that body, wheels and power transmitting sys- tem are free from abnormal noise and abnormal vibra- WARNING: tion or any other abnormal condition. With vehicle parked on a fairly steep slope, make sure nothing is in the way downhill to avoid any personal injury or property damage. Refer to “Air Bag System Components and Wiring Location View” un- der “General Description” in air bag system section in order to confirm whether you are perform- ing service on or near the air bag system components or wiring. Defroster nozzle 11. Their operation is controlled by selecting the positions of the control levers and mode select switch on the instrument panel. Switch Lever C Lever B. Ventilating air is drawn into the interior from the intake grille and drawn out from the ventilator outlet provided at each side of the body outer panel. D Blower resistor faulty D Check continuity. D Blower motor faulty D Replace motor. INSPECTION Check blower fan motor resistor for each terminal-to-terminal con- tinuity. If there is no continuity, replace blower fan motor resistor. INSTALLATION Reverse removal procedure for installation. D Never rest a steering column assembly on steering wheel with air bag (inflator) module face down and col- umn vertical. D When installing each part, be careful not to catch any cable or wiring harness. Refer to “Disab- ling Air Bag System” in SECTION 9J. 3) Remove control lever knobs and center garnish mounting screw. Refer to “HEATER CONTROL LEVER ASSEMBLY” in this section. 2) Remove heater control cables from control lever assembly. D After installing control cables, be sure that control knobs move smoothly and stop at proper position. Refer to “Disabling Air Bag System” in SECTION 9J. 3) Disconnect mode actuator coupler. 4) Disconnect mode actuator rod from heater unit. 5) Remove mode actuator from heater unit. Refer to “Air Bag System Components and Wiring Location View” un- der “General Description” in air bag system section in order to confirm whether you are perform- ing service on or near the air bag system components or wiring. This Section covers the description, charg- ing of refrigerant, etc.MAJOR COMPONENTS AND REFRIGERANT FLOW OF AIR CONDITIONING SYSTEM For LH Vehicle For RH Vehicle: Liquid. Thus compressed gas is sent to the condenser where it is changed into liquid refrigerant whose heat of vaporization can be reused. Compressors used for the air conditioning of vehicle include recip- rocating-, vane rotary-, swash plate-, and wobble plate- types. Condenser fan motor relay 5. Ignition switch 15. Condenser fan motor relay 5. Ignition switch 15. Compressor relay 6. Discharg- ing it into atmosphere would cause adverse effect to environments. NOTE: When handling recovery and recycling equipment, be sure to follow the instruction manual for the equipment. Described here is a method to charge the air conditioning system with refrigerant from the refrigerant service con- tainer. When charging refrigerant recovered by using the refrigerant recovery and recycling equipment (when recycling refrigerant), follow the procedure described in the equipment manufacturer’s instruction manual. Thus open refriger- ant container valve to purge the charging line. Then open the low pressure-side valve. Common sense should be used in performing any refrigerant leak test, since the need and extent of any such test will, in general, depend upon the nature of a complaint and the type of a service performed on. Magnetic clutch does not engage properly a) Fuse blown Replace fuse and check for short.Clogged condenser fins should be washed with water, and should be dried with compressed air. NOTE: Be careful not to damage condenser fins. Installation Reverse removal sequence to install condenser, noting following point. Refer to “Disabling Air Bag System” in Section 9J. 3) Recover refrigerant by using recovery and recycling equip- ment. Be sure to follow the instruction manual for the equip- ment. If found clogged, use com- pressed air to clean the fins. NOTE: Do not use water for cleaning of evaporator. 2) Check inlet and outlet fittings for crack or scratch. Repair them as required. The electrical characteristic is shown left. When temperature is lower than specified, amplifier makes mag- net clutch turn off to prevent evaporator from frosting. Removal Refer to items REMOVAL and DISASSEMBLY in the section of EVAPORATOR. Retighten or replace loose clamp as required, if any. Removal 1) Recover refrigerant by using recovery and recycling equip- ment. DUAL PRESSURE SWITCH This vehicle is equipped with switch which operates according to high or low pressure. Inspection 1) Check switches for continuity at normal temperature (approx. Compressor body assembly 12. Special Tool (C): 09900-06107 7) Remove magnet clutch lead wire clamp screw, and disconnect magnet clutch read wire. 8) Remove magnet clutch with puller. NOTE: Be careful not to remove cylinder from case. PROCEDURE 1) Connect high and low side charging hose of manifold gauge set to hose fittings of compressor. 2) Run engine, and keep compressor speed at 2,000 rpm. Example: If dry-bulb temperature is 905F and wet-bulb temperature is 785F, the relative humidity is HOW TO READ RELATIVE HUMIDITY (5C) Measure wet-bulb temperature and dry-bulb. Please observe all WARNINGS and SERVICE PRECAUTIONS in SEC- TION 9J under “On-Vehicle Service” and the Air Bag System Component and Wiring Location view in SECTION 9J before performing service on or around Air Bag System Components or Wiring. To avoid using the wrong symptom, always road test the vehicle first. Proceed with the following preliminary inspection and correct any defects which are found. Vibration 2. Loose wheel bearings. Replace wheel bearing. 3. Some of them are: incorrect inflation pressures, lack of tire rotation, driving habits, im- proper alignment. If the following conditions are noted, rotation is necessary: 1) Front tire wear is different from rear. Lead is usually caused by: 1) Incorrect alignment. 2) Uneven brake adjustment. An additional item to be checked is the possibility of tire lead due to worn or improperly manufactured tires. “Lead” is the deviation of the vehicle from a straight path on a level road without hand pressure on the steering wheel. If steering angle is not correct, check if right and left tie rods are equal in length ( “A”. Refer to “Air Bag System Components and Wiring Location View” under “General Description” in air bag system section in order to confirm whether you are per- forming service on or near the air bag system components or wiring. When the steering wheel is turned, the motion is transmitted to the steering shaft, shaft joint and then to the pinion. Since the pinion teeth mesh with teeth on rack, the motion is further transferred to the rack and changed to linear motion. Grease: SUZUKI SUPER GREASE E (99000-25050) 2) Install rack plunger, rack plunger spring, rack damper screw to steering case in direction shown. Tighten rack damper screw to specified torque. Special Tool (43 mm socket) (A): 09944-26011 3) Tap on position as shown with plastic hammer to separate pin- ion assembly from housing. Special Tools (A): 09921-20200 (B): 09930-30104. Or housing (pipe) may come off gear case. For this work, be sure to use the specified spe- cial tool. Inspect each boot for tear. A torn boot allows entry of dust and wa- ter which can cause wear to steering rack and pinion to produce noise as well as rust to result in malfunction of steering system. In either case, if found defective, replace. 1. Rack plunger 2. Plunger spring STEERING PINION 1) Inspect pinion teeth surface for wear or damage. 2) Inspect oil seal for damage. Refer to “Air Bag System Components and Wiring Location View” under “General Description” in air bag system section in order to confirm whether you are per- forming service on or near the air bag system components or wiring. It is an integral type with the rack and pinion gears and the control valve unit, hydraulic pressure cylinder unit all built in the steering gear box. Main components of the cylinder sec- tion are a gear box, a rack and a tube and those of the valve section are a valve case, a sleeve and a stub shaft. The steel ball in the relief valve is under the hydraulic pressure in the circuit coming through orifice A. If found defective, repair or replace. Check steering wheel for play, holding car in straight forward condi- tion on the ground and with engine stopped. Push 2) Check that belt is free from any damage and properly fitted in pulley groove. If any of above conditions are found replace generator belt by refer- ring to “GENERATOR BELT”. Tighten each flare nut to specified torque. Close gauge valve gradually while watching pressure increase in- dicated by gauge and take reading of relief pressure (maxi- mum hydraulic pressure).STEERING SHAFT JOINT Check each shaft joint for wear, breakage and any other damage and if any, replace it with a new one. AIR BLEEDING PROCEDURE 1) Jack up the front end of vehicle and apply safety stands. CAUTION: Be sure to set front wheels (tires) in straight direction and remove ignition key from key cylinder before the. Position lock nut to marking made in removal. Marking made in removal. NOTE: When tie rod was replaced, measure length “A” on re- moved tie rod and use it on new replacement tie rod so as to position lock nut properly. As fluid flows out of disconnected joints, put a container under joints or a plug to hose. CAUTION: When disconnecting, take care not to cause damage to generator. D Check clearance between rotor and vane. Clearance: Standard 0.01 mm (0.0004 in.) Limit 0.06 mm (0.0023 in.) Replace pump assembly if any defect is found in above checks. 1. Tightening Torque (b): 28 N m (2.8 kg-m, 20.0 lb-ft) 18) Apply power steering fluid to relief valve (flow control valve). 19) Install relief valve (flow control valve) to pump body. They must be replaced with one of the same part number or with an equivalent part if replacement becomes necessary. Refer to “STEERING WHEEL” earlier in this section. 3) Remove hole cover. 1. Hole cover 4) Remove steering column cover screws (3 pcs). If it is damaged, replace. INSTALLATION 1) Install combination switch to steering column. Refer to “STEERING WHEEL” earlier in this section. 9) Connect battery negative cable. STEERING COLUMN CAUTION: D Once the steering column is removed from the vehicle, the column is extremely susceptible to damage. After disconnecting, turn ignition switch to “LOCK”. If it is shorter than specified length, replace column assembly with new one. Length “b”: 513 mm (20.20 in.) 3) Check steering shaft joints and shaft for any damages such as crack, breakage, malfunction or excessive play. NOTE: After tightening column nuts, bolt to steering shaft upper joint should be tightened.Refer to “STEERING COLUMN” ear- lier in this section. 1. Steering column 2. Steering lock 3) Using center punch as shown, loosen and remove steering lock 1. Then insert lower joint shaft into upper joint. 2) Be sure that front wheels and steering wheel are in straight- for- ward state and insert lower joint into steering pinion shaft. Failure to follow procedures could result in possible air bag deployment, personal injury or other- wise unneeded air bag system repairs. D The ignition switch and lock are mounted conveniently on this column. Be sure to follow the instructions. WARNING: When performing service on or around air bag system components or air bag system wiring, follow the procedures listed below to temporarily disable the air bag system. Failure to follow them could cause a damage to the air bag (inflator) mod- ule or result in personal injury. D Air bag being deployed D Trim cover (pad surface) being cracked D Wire harness or connector being damaged D Air bag (inflator) module being damaged or having been ex- posed to strong impact (dropped) 1. NOTE: Contact coil can turn about 5 turns at maximum, that is, if it is at the center position, can turn about two and a half turns both clockwise and counterclockwise. D Dropping the column assembly on its end could col- lapse the steering shaft. D Loosen the plastic shear pins which maintain column length. WARNING: Never rest a steering column assembly on the steer- ing wheel with the air bag (inflator) module face down and column vertical. Otherwise, personal inju- ry may result. INSPECTION NOTE: Vehicles involved in accidents resulting in body damage,. Then insert upper side joint of steering column into lower joint shaft. 1. Refer to “Contact Coil and Combination Assembly” earlier in this section. Refer to “Disabling Air Bag System” un- der “Service Precautions” earlier in this section. 3) Remove steering column. Refer to “STEERING COLUMN” ear- lier in this section. Should it have been turned and contact coil (on combina- tion switch) have got out of its centered position, it needs to be centered again. They must be replaced with one of the same part number or with an equivalent part if replacement becomes necessary. The upper end of a strut is anchored to the vehicle body by a strut support. The strut and strut support are isolated by a rubber mount. A strut bearing is also installed a little lower to the rubber mount. This will make disassembly easier. Note, however, nut must not be removed at this point. REMOVAL 1) Hoist vehicle, allowing front suspension to hang free. Insert bolts in such a direction as shown. Please note that all work should be performed by a qualified person. Check out this home repair tutorial video that demonstrates how to repair a Dyson vacuum cleaner. Dyson DC14 Full Gear vacuum. To our guests watching: You must be logged in to the forums to see the photos. Dyson Advice, Dyson Spare Parts, Dyson Service Manuals, Dyson User Manuals, Dyson Service Guide and Dyson DIY Repairs.How To Repair Your Dyson Vacuum Cleaner. How To Repair Your Dyson Vacuum Cleaner. Call: 07986 474499. This guide will show you the necessary steps to replace the motor in your Dyson DC14 Vacuum. The former type of strategy focuses on obtaining approvals most rapidly. The latter type involves attempts to achieve the greatest market share by influencing decision leaders, planning symposia, developing an approach to publications, and conducting appropriate clinical trials, including those evaluating quality-of-life and pharmacoeconomic endpoints. Ideally, the regulatory strategies chosen will attain both goals. Interacting with Company Staff Regulatory affairs staff should be present on all project teams and all relevant committees within the organization. Thus, the staff can provide regulatory input, answer questions, and instill relevant regulatory concepts to enhance drug development. Frequent personal interactions with company staff throughout the organization are required to fulfill the mission of regulatory affairs. Interacting with Regulatory Authorities The scope of interactions between regulatory affairs professionals and regulatory authorities depends on the country involved, the company’s philosophy, and the type of interaction being considered. Regulatory affairs professionals often act as a liaison between personnel in the company (e.g., medical staff, technical development staff) and regulatory authorities. This coordinating role is crucial because it prevents people in the company independently or semi-independently interacting with regulatory authorities. That approach would undoubtedly lead to major problems if different people said different things to regulatory authorities, or if the statements of different people were understood differently than intended. Regulatory affairs personnel document all interactions with regulators, whether in writing, on the telephone or electronically. Personnel issues concerning one or more clinical investigators who conducted a trial(s) 11. Changes to a protocol (e.g., amendments) 12. Labeling issues 13. Preclinical requirements 14. Chemistry and manufacturing issues (e.g., adequacy to support later phase studies) 15. Special priority for the review (e.g., Treatment IND, accelerated approval, Subpart E designation) 16. Compliance issues (e.g., questions about monitoring a clinical trial) 17. International issues (e.g., import-export issues, inspection of various facilities) 18. Whether or how to file an electronic IND or NDA Table 85.3 Selected topics that may be discussed between a regulatory affairs department and regulatory authorities on marketed drugs 1. Adverse events reported to the company 2. Changes in labeling requested by the company or by the regulatory authority 3. Annual report of activities on each drug 4. Submissions requesting a new indication, formulation, or change to over-the-counter status 5. Import or export of drugs 6. Definitions of important terms or concepts affecting a drug 7. Interpretations of law, regulations, guidelines, or monographs affecting a drug 8. Clarifications of comments made by regulatory authority staff at meetings or in letters sent to the company 9. Advertising issues 10. Other marketing issues 11. Product problems 12. Postmarketing studies 13. Although regulations differ around the world, major steps toward harmonization have been and continue to occur, primarily through the aegis of the ICH. Preparing and submitting regulatory documents to a regulatory authority may be viewed as a publication activity. This activity involves collecting manuscripts and reports, and then copyediting them to assure within and between section consistency in terminology and data plus deciding if any explanation (or White Paper) is required to indicate how the data fit the overall picture. Once those steps are completed, it is necessary to paginate the documents, indexing the contents, adding cross-references, copying and binding them, and then distributing the copies ( Table 85.5 ). This is an extremely complex and difficult process to carry out efficiently and cannot be done rapidly. Often, the parts of a submission that are available first can be processed before the later sections are delivered. However, the final reviews and data consistency checks, when omitted, will almost always slow the Agency’s review by introducing unnecessary questions. Once errors and negative agency interpretations find their way into the regulatory file there is no way to remove them. Compassionate plea submission describing drug sent to a physician for a specific patient 11. Response to questions received on a regulatory submission 12. Request for a meeting with a regulatory authority group 13. Submission of information or data for consideration by an advisory committee to the regulatory authority 14. Request for a clarification of something received (e.g., letter, telephone call) from the regulatory authority 15. Appeal of a decision made by the regulatory authority 16. Request for marketing exclusivity or another specific regulatory pathway (e.g., orphan drug) CTX, Clinical Trial Exemption; BLA, Biologic License Application. The submission should also be easy for reviewers to follow in terms of scientific logic and internal consistency (e.g., the accepted practice is to proceed in order from small to large animals in presenting data and results for toxicology and pharmacokinetic studies, Phase 1 clinical data are ordinarily presented separately from the rest of the clinical data). Even though the European expert reports are not required in the CTD, they are still sometimes included in regulatory dossiers. The style of expert reports should adhere to preferences of the regulators. Every page of an NDA should have a document page number and an NDA page number, and the application must comply with appropriate formats. Some of the problems previously encountered in this process (e.g.