nocompoundash0001 covance investigatormanual_eu_revised_04 feb 2013

Covance CLS Investigator Manual

Covance Central Laboratory Services 2008 Covance CLS. All rights reserved.www.covance.com/central_lab/info.php Laboratory regulatory certifications available on Covance website

Janssen Research & Development, LLC.Protocol: NOCOMPOUNDASH0001

Covance Project Number: 205263

Manual Created: 14 June 2010Manual Revised: 4 February 2013

Indianapolis8211 SciCor DriveIndianapolis, IN46214-2985 USATel. (317) 271-1200 (local calls)Fax: (317) 273-4030

GenevaRue Mose-Marcinhes 71217 Meyrin/Genve-CHTel: +41 58-822-7000 Fax: +41 58-822-6999

Singapore1 International Business Park#05-12A/B The SynergySingapore 609917Tel. 65-6560-8793 Fax. 65-6565-5901

Shanghai1st Floor, No. 6 Building151 Li Bing RdZhangjiang Hi-Tech ParkShanghai 201203ChinaTel: +86 21 51371111Fax:+86 21 51371301

TokyoCB Labc/o BML General Laboratory1361-1 MatobaKawagoe-shiSaitama 350-1101 JapanJapan Toll free: 0120-123-905Direct line: 03-5159-3426Fax: 03-5250-0360

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Disclaimer: The Created Version Date and the Revised Version Date on the cover of the manual refer to either the original publication of the manual or the customer requested changes to the protocol specifi c pages. The dates on the Covance standard pages are not necessarily representative of the Revised Version Date, as the updates of these pages are due to Covance internal changes or regulatory changes, which can occur at anytime.

TABLE OF CONTENTS

2008 Covance CLSEnglish_TableOfContents_Update: 20100614

Schedule Visit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Section 1Kit InformationStabilitiesHoliday Considerations/Customs Closures

Collect Samples . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Section 2Laboratory Visit ScheduleAnalytes by GroupsToxicology Cut-OffsCentrifuge InstructionsSpecimen Collection ProceduresCoagulation TestingPaxGene InstructionsBlood Smear PreparationDraw Tube Adapter ProceduresUrine Pregnancy InstructionsInstructions for Completing Requisition FormsProject Specifi c Requisition Forms

Pack and Ship . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Section 3General InformationCourier Contact NumbersDangerous Goods Training InformationPackaging and Shipping of Samples

Resupply . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Section 4General Information - Supply/ResupplyAdditional Kits/Material Reorder Form

Get Result. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Section 5Reference Ranges/Alerts and FlagsProject Specifi c Reference Ranges and/or Alerts and Flags

Get Help . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Section 6 Covance CLS Customer Service Contact Numbers

Laboratory Certifi cations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Section 7

Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Section 8

Archived Pages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Section 9

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Section 10

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1Page: 3205263_TMEA

English_Kit Information_Update: 20110204 2003 Covance CLS

KIT INFORMATION

!NOTE: To obtain the highest quality specimens possible, it is recommended all collection supplies

be stored between 4C to 25C (39F to 77F).

! Kits are protocol, investigator and visit speci c.

Select the correct kit accordingly.

Please check kit expiration dates before using the kit!Some tubes used for the collection of samples have expiration dates. These dates are defined by tube manufacturers.To ensure the validity of the tubes contained in the collection kit, expiration dates are printed on the outside of the kit box. The expiration date of each kit corresponds to the shortest expiration date of the tube(s) within the kit.

!Please do not collect specimens in expired containers! Specimens received in an expired container which includes an additive will be canceled as: Sample drawn in expired tube: Testing not performed. If you have expired tubes please call Covance CLS to have these kits replaced and your inventory updated.

A unique accession number is assigned to each kit and its requisition form. Within the kit, specimen containers and the requisition have the same accession number (bar code).

!Do not interchange the tubes and/or requisition forms between kits!

Complete the labels with appropriate identi ers (screening number and/or patient number) using a black ball point or indelible ink pen.

Each container label is pre-printed with an internal Covance code, which is to be its primary source of identi cation.

Bulk SuppliesDepending on your protocol, additional items may be provided. For some studies, no bulk supply is provided.

Note: Information about investigator performance in connection with the use and/or return of materials in any laboratory test kit will be collected and used by Covance and/or its affiliates to help evaluate clinical studies and to evaluate investigators for future clinical studies.

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English_Stabilities for Analytes in Specimens_Update: 20061030 2003 Covance CLS

STABILITIES FOR ANALYTES IN SPECIMENS

Listed below are stabilities at ambient storage.

Covance Central Laboratory Services must receive specimens within the stability period established by our laboratory in order to test the specimen.

If you have questions relating to analytes not listed, please call us.

Analyte Hours Days Analyte Hours DaysChemistry Group Total Bilirubin Alkaline Phosphatase LDH GGT ALT (SGPT) AST (SGOT) Urea Nitrogen Creatinine Uric Acid Phosphorus Calcium Glucose Total Protein Albumin CK Electrolytes Sodium Potassium Bicarbonate Chloride Magnesium Lipids Triglycerides Cholesterol HDL Cholesterol LDL Cholesterol

721201201207272120120120120120721207272

12012072120120

120120120120

355533555553533

55355

5555

Urinalysis Color Clarity Specific Gravity pH Protein Glucose Ketones Bilirubin Urobilinogen Blood Nitrite Leukocyte Esterase Microscopic Hematology Hemoglobin Hematocrit RBC MCV MCH MCHC WBC Neutrophils Bands Lymphocytes Monocytes Eosinophils Basophils Platelets Morphology

96969696969696969696969696

726072607260727272727272727272

4444444444444

32.532.532.5333333333

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2010 Covance CLS

CUSTOMS CLOSED/PUBLIC HOLIDAYS

English_Custom Closed/Public Holidays 1/4_Update: 20110614

!

Important considerations

Local courier service (pickup and delivery) may be limited prior to, during and following observed holidays in the country to which you are shipping specimens. It is imperative that you check local service schedules in advance of the holiday. Listed below are important considerations when planning your patient visits during the holidays.

- Your courier service reserves the right to observe earlier than usual pick-up times during the holidays. Call your courier service for local pick-up schedules.

- During the December/National holidays, schedule your pickups in advance of the holiday where possible.

- Call early in the day to schedule your pickup.

- When a holiday is observed on Monday, avoid laboratory collections on the preceding Saturday (i.e. Labor Day). (Not applicable to Japan)

- Frozen specimens should NOT be shipped on the day before the observed holiday. Send frozen

specimens on the next available business day. (Not applicable to Japan)

- If shipping specimens on Friday, mark airway bill for Saturday delivery. (Not applicable for Japan)

- Specimens with short stabilities (eg. lymphocyte subsets, reticulocyte counts, etc.) should not be collected on the day prior to the holiday. (Not applicable to Japan)

- For sites with 24 hours delivery time to Covance, do not schedule any shipment 24 hours before one of the dates on the next pages. (Not applicable for Japan)

- For sites with 48 hours delivery time to Covance, do not schedule any shipment 48 hours before one of the dates on the next pages. (Not applicable for Japan)

Holiday reminders are also available on the Covance website:http://www.covance.com/investigators/holidays.pdf

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English_Custom Closed/Public Holidays 2/4_Update: 20121221 2010 Covance CLS

CUSTOMS CLOSED/PUBLIC HOLIDAYSCALENDAR

US, Canada, Puerto Rico and Latin America (specimens sent to Indianapolis)

2013 2014 2015

1 January 1 January 1 January New Years Day27 May 26 May 25 May Memorial Day4 July 4 July 4 July 2 Independence Day2 September 1 September 7 September Labor Day28 November 1 27 November 1 26 November 1 Thanksgiving Day29 November 1 28 November 1 27 November 1 Thanksgiving Day25 December 25 December 25 December Christmas Day

For sites in US and CanadaIf you ship specimens on a Thursday that is a holiday in the United States, you should mark Saturday delivery on the airway bills.

1 Limited operations within Covance this day due to Thanksgiving period.

2 July 4, 2015 (the legal public holiday for Independence Day), falls on a Saturday. For most Federal employees, Friday, July 3, will be treated as a holiday for pay and leave purposes.

Europe, Middle East and Africa (specimens sent to Geneva)

2013 2014 2015

1 January 1 January 1 January New Years Day29 March 18 April 3 April Good Friday1 April 21 April 6 April Easter Monday9 May 29 May 14 May Ascension Day20 May 20 May 24 May Whit Monday1 August 1 August 1 August Swiss National Day5 September 11 September 10 September Jene Genevois24 December 24 December 24 December Christmas Eve25 December 25 December 25 December Christmas Day31 December 31 December 31 December New Years Eve

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Asia, Australia and New Zealand (specimens sent to Singapore)

2013

1 January New Years Day10 February * Chinese New Year11 February * Chinese New Year29 March Good Friday1 May Labour Day24 May Vesak Day8 August Hari Raya Puasa9 August National Day15 October Hari Raya Haji3 November **, *** Deepavali25 December Christmas Day

* As Chinese New Year falls on Sunday 10 February 2013 and Monday 11 February 2013, the next day, Tuesday 12 February 2013, will be a public holiday.Taiwan Customs are closed on Saturday/Sunday.** The following Monday will be a public holiday.*** Subject to change

China (specimens sent to Shanghai)

2013

30 Dec. 2012 - 1 January New Years Day19-15 February Spring Festival24-6 April Tomb Sweeping Day329 April - 1 May Labor Day410-12 June Dragon Boat Festival519-21 September Mid-Autumn Festival61-7 October National Days7

1 December 29 (Saturday) is adjusted as working day.2 February 16 (Saturday) and February 17 (Sunday) are adjusted as working day3 April 7 (Sunday) are adjusted as working day4 April 27 (Saturday) and April 28 (Sunday) are adjusted as working day5 June 8 (Saturday) and June 9 (Sunday) are adjusted as working day6 September 22 (Sunday) is adjusted as working day7 September 28 (Saturday) and September 29 (Sunday) are adjusted as working day

The courier may be ordered any calendar day of the year. However, as much as possible, please avoid shipping samples on Saturdays and Sundays.

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Japan (specimens sent to Tokyo)

2013 2014

1 January 1 January New Years Day14 January 13 January Coming of age Day11 February 11 February National Foundation Day20 March 21 March Vernal Equinox29 April 29 April Showa Day3 May 3 May Constitution Memorial Day4 May 4 May Greenery Day5 May 5 May Childrens Day15 July 21 July Marine Day16 September 15 September Respect of the Aged Day23 September 23 September Autumnal Equinox14 October 13 October Sports Day3 November 3 November Culture Day23 November 23 November Labor Thanksgiving Day23 December 23 December Birthday of the Emperor

(1) With the exception of New Year Bank Holidays, if a holiday falls on a Sunday, the following day is treated as a holiday instead.(2) When there is a single day between two national holidays, its also taken as a holiday.

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LABORATORY VISIT SCHEDULE FOR PROTOCOL NOCOMPOUNDASH0001Janssen Research & Development, LLC.

English_Visit Test Schedule_Update: 20130204 2008 Covance CLS

VISIT Screen - HealthyBaseline -

HealthyBronchoscopy -

HealthyScreen -

AsthmaticBaseline - Asthmatic

Bronchoscopy - Asthmatic(optional)

3 Month Biomarker-- Asthmatic

OCCURRENCE Day -14 to -10 Day 0 Day 7-14 Day -14 to -10 Day 0 Day 7-14 Month 3TEST GROUPSChemistry Panel X XHematology & Differential Panel X XUrine Macro Panel X XHIV 1/HIV-2 Antibody X XHepatitis Panel X XCoagulation Panel X XPhadiatop X XComprehensive Drug Screen X XCotinine, Urine X XDNA IsolationA

Reflex(es)Direct Bilirubin R RCKMB R RTroponin I R RUrine Micro Panel R RWestern Blot, HIV-1 R RWestern Blot, HIV-2 R RAmphetamine Confirmation R RBarbiturates Confirmation R RBenzodiazepines Confirmation R RCannabinoid Confirmation R RMethadone Confirmation R ROpiate Confirmation R RCocaine Confirmation R RAlpha-1 AntitrypsinAntidepressant Confirmation R RSpecimen ManagementSM1 PD Serum X X X X XSM2 PD Urine X X X X XSM3 RNA X X XSM5 Biopsy - Formalin X XSM6 Biopsy - RNA X XSM7 Bronchial Brush X XSM8 Sputum SupernatantB

SM9 Sputum CytospinB

SM10 Sputum Cell PelletB

SM13 Nasal Brushing

X Mandatory testingR Reflex testing

A Refer to DNA kitB Refer to Sputum kit

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VISIT6 Month

Biomarker-- Asthmatic

12 Month Biomarker-- Asthmatic

DNA Sputum Retest Screen Baseline Bronchoscopy Nasal Brushing

OCCURRENCE Month 6 Month 12 - - - Day -14 to -10 Day 0 - -TEST GROUPSChemistry Panel O XHematology & Differential Panel O XUrine Macro Panel O XHIV 1/HIV-2 Antibody O XHepatitis Panel O XCoagulation Panel O XPhadiatop O XComprehensive Drug Screen O XCotinine, Urine O X X XDNA IsolationA XReflex(es)Direct Bilirubin R RCKMB R RTroponin I R RUrine Micro Panel R RWestern Blot, HIV-1 R RWestern Blot, HIV-2 R RAmphetamine Confirmation R RBarbiturates Confirmation R RBenzodiazepines Confirmation R RCannabinoid Confirmation R RMethadone Confirmation R ROpiate Confirmation R RCocaine Confirmation R RAlpha-1 Antitrypsin O RAntidepressant Confirmation R RSpecimen ManagementSM1 PD Serum X X O X XSM2 PD Urine X X O X XSM3 RNA X X O XSM5 Biopsy - Formalin XSM6 Biopsy - RNA XSM7 Bronchial Brush XSM8 Sputum SupernatantB XSM9 Sputum CytospinB XSM10 Sputum Cell PelletB XSM13 Nasal Brushing X

X Mandatory testingO Optional testingR Reflex testing

A Refer to DNA kitB Refer to Sputum kit

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Kit - DNAThis kit should be used for subjects who consent to Pharmacogenomic (DNA) testing.

Kit - SputumThis kit should be used for both Healthy and Asthmatic Sputum testing.

Kit - RetestThis kit can be used:- for repeat or follow-up testing- to redo analyses at any time during the trial or- to substitute for any kit, if you do not have the appropriate kit in stock. If so, please cross through Retest and write the visit name on the requisition form. Make sure that you order all tests required for the visit being performed.

Screen Healthy, Baseline Healthy and Bronchoscopy Healthy are required visits for Healthy subjects only.

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ANALYTES BY GROUPS FOR PROTOCOL NOCOMPOUNDASH0001Janssen Research & Development, LLC.

English_Analytes By Groups_Update: 20130204 2008 Covance CLS

REFLEX TESTING * If Total Bilirubin > 1.2 mg/dL (Conv.) or 21 umol/L (SI), then a Direct Bilirubin will automatically be

performed.

** If CK > 198 U/L (both Conv. & SI), then CKMB and Troponin I will automatically be performed.

*** If Urine Macro Panel Blood = Trace, +1, +2, or +3, OR Protein = Trace, +1, +2, +3, +4, OR Ketones = Trace, +1, +2, +3, +4, OR Urobilinogen = +1, +2, +3, +4, OR Bilirubin = +1, +2, +3, +4, OR Nitrite = +1, +2, OR Leukocyte Esterase = Trace, +1, +2, +3, then a Urine Micro Panel will automatically be performed.

**** If the HIV-1/HIV-2 Antibody = Reactive, then a Western Blot, HIV-1 will automatically be performed. If the Western Blot, HIV-1 is non-reactive or indeterminate, then Medical Affairs will determine whether the Western Blot, HIV-2 is necessary.

CHEMISTRY PANELTotal BilirubinAlkaline PhosphataseALT (SGPT)AST (SGOT)LDHUrea NitrogenCreatinineGlucoseCalciumPhosphorusTotal ProteinAlbuminCKSodium PotassiumBicarbonateChloride

DIRECT BILIRUBIN*

TROPONIN I**

CKMB**

HEPATITIS PANELHepatitis B surface AntigenHepatitis C Antibody

COAGULATION PANELProthrombin TimeaPTT

COTININE, URINE

HEMATOLOGY & DIFFERENTIAL PANELHemoglobinHematocritRBCRBC MorphologyWBCNeutrophils (%, abs)Lymphocytes (%, abs)Monocytes (%, abs)Eosinophils (%, abs)Basophils (%, abs)Platelets

URINE MACRO PANELSpecific GravitypHProteinGlucoseKetonesBilirubinUrobilinogenBloodNitrite Leukocyte Esterase

URINE MICRO PANEL***Microscopic

HIV-1/HIV-2 ANTIBODY

WESTERN BLOT, HIV-1****

WESTERN BLOT, HIV-2****

PHADIATOP

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ANALYTES BY GROUPS FOR PROTOCOL NOCOMPOUNDASH0001Janssen Research & Development, LLC.

English_Analytes By Groups_Update: 20130204 2008 Covance CLS

SM1 PD SERUMPD Serum

SM2 PD URINEPD Urine

SM3 RNARNA

SM4 DNADNA

SM5 BIOPSY FORMALINBiopsy

SM6 BIOPSY - RNABiopsy

SM7 BRONCHIAL BRUSHBronchial Brush

SM8 SPUTUM SUPERNATANTSputum Supernatant

SM13 NASAL BRUSHINGNasal Brushing

ALPHA-1 ANTITRYPSIN *****

SM9 SPUTUM CYTOSPINSputum Cytospin

SM10 SPUTUM CELL PELLET (for mRNA)Sputum Cell Pellet

DNA ISOLATIONA260A280Hydration VolumeSample VolumeConcentrationPurityTotal YieldAliquot 1 ConcentrationAliquot 1 VolumeAliquot 1 YieldAliquot 2 ConcentrationAliquot 2 VolumeAliquot 2 Yield

REFLEX TESTING ***** If the question Does subject have COPD? is answered Yes, then an Alpha-1 Antitrypsin will

automatically be performed.

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URINE DRUG SCREEN* FOR PROTOCOL NOCOMPOUNDASH0001Janssen Research & Development, LLC.

* If a urine drug screen results positive, a confirmation test will automatically be performed.

English_Urine Drug Screen_Update: 20130204 2008 Covance CLS

COMPREHENSIVE DRUG SCREENAmphetamines ScreenAntidepressants ScreenBarbiturates ScreenBenzodiazepines ScreenCannabinoids ScreenCocaine ScreenMethadone ScreenOpiates Screen

AMPHETAMINE CONFIRMATIONAmphetamineMethamphetamine

ANTIDEPRESSANT CONFIRMATIONAmitriptylineDesipramineDoxepin and/or metabolite(s)ImipramineNortriptyline

BARBITURATE CONFIRMATIONAmobarbitalButabarbitalButalbitalPentobarbitalPhenobarbitalSecobarbital

OPIATE CONFIRMATIONCodeineDihydrocodeineHydrocodoneHydromorphoneMorphineOxycodone6-MAM

METHADONE CONFIRMATIONMethadone

COCAINE CONFIRMATIONCocaine and/or metabolites

CANNABINOID CONFIRMATIONCannabinoids

BENZODIAZEPINE CONFIRMATIONAlprazolam and/or metabolite(s)Clonazepam and/or metabolite(s)DiazepamN-DesmethyldiazepamFlunitrazepam and/or metabolite(s)LorazepamNitrazepam and/or metabolite(s)OxazepamFlurazepam and/or metabolite(s)Temazepam

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English_Centrifuge Instructions_Update: 20091002 2008 Covance CLS

CENTRIFUGE INSTRUCTIONS

Recommendations regarding the proper use of centrifuge: Centrifuge operators should evaluate the size of collection tubes compared to the buckets that are used in the centrifuge. Most centrifuges have different types of buckets available for purchase from the vendor. Tubes requiring centrifugation must rest on the bottom of the bucket that is used. If a tube is short and does not rest on the bottom of the bucket that is used, a spacer provided by the centrifuge vendor should be inserted into the bucket. Alternatively, a different bucket which allows the tube to rest on the bottom should be used. Warning: if the bottom of the tube does not rest on the bottom of the centrifuge bucket, the cap may loosen or come off during centrifugation. Equation for calculating the relative centrifugal forceCovance CLS recommends serum and plasma samples centrifuge at 1500 to 2000 x g for 15 minutes. Any deviations to these recommendations will be listed on your laboratory requisitions. F: gravitational force [g] R: radius measured from the center of rotation to the bottom of tube in the rotor [cm] N: speed of the centrifuge rotor [rpm = rotation per minute] Example: with a radius of 10 cm and 1000 g the required speed is: N= 2990 rpm

Using the RCF Nomograph To determine the relative centrifugal field (RCF), place a straightedge on the nomograph connecting the known speed (rpm) and the known rotating radius. The point at which the straightedge intersects the RCF axis is the field. For example, if the rotating radius is 10 cm and the speed is 3,000 rpm, the relative centrifugal field is 1,000 g (gravity)

If the field and the radius are known, the corresponding speed can be determined.

To calculate RCF RCF = 0.00001118 r N 2 RCF = relative centrifugal field (gravities) r = rotating radius (centimeters) N = rotating speed (revolutions per min)

The distance measured from the rotor axis to the tip of the liquid inside the tubes at the greatest horizontal distance from the rotor axis is the rotating tip radius. The radius is listed for your convenience in the speed and force tables.

Rotating Axis

ROTATING RADIUS

ANGLE ROTORS

ROTATING RADIUS

HORIZONTAL ROTORS

SCALE A

SCALE C

SCALE B

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SPECIMEN COLLECTION PROCEDURES FOR PROTOCOL NOCOMPOUNDASH0001 Janssen Research & Development, LLC.

Covance Container Codes

Vacutainer collection containers

Equivalent Monovette if applicable

Shipping temperature

Shipping frequency

English_Specimen Collection Procedures_Update: 20130204 2008 Covance CLS

SERUMChemistry Panel CKMB Troponin IOne 5 mL gold top serum separation tube. Fill tube completely. It is important to thoroughly mix the blood with the clotting activation agent by inverting the tube not less than ve times. Allow blood to clot for 30 minutes (tube standing upright). Centrifuge at 1500 to 2000 x g for 15 minutes until clot and serum are separated by a well-formed polymer barrier. Use pipette provided to transfer all the serum equally into the three 5 mL plastic vials labeled CHEMISTRY (ship ambient, day of collection), CK-MB FROZEN, and TROPONIN I FROZEN (freeze immediately at -20C until shipment; ship frozen on dry ice, day of collection).

Ambient

Day of collection

Frozen

HIV-1/HIV-2 AntibodyOne 2.5 mL gold top serum separation tube. Fill tube completely. It is important to thoroughly mix the blood with the clotting activation agent by inverting the tube not less than ve times. Allow blood to clot for 30 minutes (tube standing upright). Centrifuge at 1500 to 2000 x g for 15 minutes until clot and serum are separated by a well-formed polymer barrier. Use pipette provided to transfer all the serum into the 5 mL plastic vial labeled HIV-1/HIV-2.

Ambient Day of collection

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Shipping frequency


SERUMHepatitis PanelOne 2.5 mL gold top serum separation tube. Fill tube completely. It is important to thoroughly mix the blood with the clotting activation agent by inverting the tube not less than ve times. Allow blood to clot for 30 minutes (tube standing upright). Centrifuge at 1500 to 2000 x g for 15 minutes until clot and serum are separated by a well-formed polymer barrier. Use pipette provided to transfer all the serum into the 5 mL plastic vial labeled HEPATITIS.


PhadiatopOne 2.5 mL gold top serum separation tube. Fill tube completely. It is important to thoroughly mix the blood with the clotting activation agent by inverting the tube not less than ve times. Allow blood to clot for 30 minutes (tube standing upright). Centrifuge at 1500 to 2000 x g for 15 minutes until clot and serum are separated by a well-formed polymer barrier. Use pipette provided to transfer all the serum into the 5 mL plastic vial labeled PHADIATOP FROZEN. Freeze immediately at -20C until shipment.

Frozen Day of collection

Alpha-1 AntitrypsinOne 2.5 mL gold top serum separation tube. Fill tube completely. It is important to thoroughly mix the blood with the clotting activation agent by inverting the tube not less than ve times. Allow blood to clot for 30 minutes (tube standing upright). Centrifuge at 1500 to 2000 x g for 15 minutes until clot and serum are separated by a well-formed polymer barrier. Use pipette provided to transfer all the serum into the 5 mL plastic vial labeled ALPHA-1 ANTITRYPSIN.


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Shipping frequency


SERUMSM1 PD SerumOne 8.5 mL gold top serum separation tube. Fill tube completely. It is important to thoroughly mix the blood with the clotting activation agent by gently inverting the tube no less than ve times. Allow blood to clot for 30 minutes (tube standing upright). Centrifuge blood samples at room temperature within 1 hour of collection (minimum of 1500 x g for 15-20 minutes) until clot and serum are well separated. Use pipette(s) provided to transfer all of the separated serum (use 1 new pipette per sample) into the appropriately labeled cryotube vials. Distribute serum equally into all cryotube vials provided for the individual blood sample. Freeze as soon as possible at approximately -20C or lower until shipment in a non-automatically defrosting freezer. Do not exceed 30 minutes for the time between centrifuging the blood and freezing the serum. Ship frozen on dry ice to Covance CLS day of collection.


PLASMACoagulation PanelDraw this tube last.One 1.8 mL blue top sodium citrate tube. Fill tube completely. Mix immediately by gently inverting the tube at least 8 to 10 times. Centrifuge at 1500 to 2000 x g for 15 minutes until cells and plasma are well separated. Use pipette provided to transfer all the plasma into the 3 mL plastic vial labeled COAGULATION PANEL FROZEN. Freeze immediately at -20C or -70C until shipment.


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Shipping frequency


URINEUrine Macro PanelOne 10 mL orange top urine tube with preservative tablet. Transfer specimen from standard urine collection cup into tube labeled URINALYSIS. Do not ll above 9 mL mark. Screw cap on tightly.


Cotinine, UrineOne 10 mL yellow top urine tube without preservative. Transfer specimen from standard urine collection cup into tube labeled COTININE, URINE FROZEN. Do not ll above 9 mL mark. Screw cap on tightly. Freeze immediately at 20C until shipment.


Comprehensive Drug ScreenOne 30 mL urine tube without preservative tablet. Transfer specimen from standard urine collection cup into tube labeled URINE DRUG SCREEN. Do not ll above 30 mL mark. Screw cap on tightly.


SM2 PD UrineSee Urine Collection Instructions in the Study Reference Manual supplied by Centocor.

Transfer 1 mL of urine from sterile urine collection cup into the four appropriately labeled 1.8 mL, cryovials with the yellow bar, labeled SM2 PD Urine and into the 2 mL amber cryovial pre lled with BHT. Secure screw cap on tightly. Freeze immediately at -80C until shipment. Ship frozen on dry ice to Covance CLS day of collection.


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Shipping frequency


WHOLE BLOODHematology & Differential PanelDraw whole blood samples last except when collecting coagulation group at the same visit.One 2 mL lavender top tube. Fill tube completely. Mix immediately by gently inverting the tube at least 8 to 10 times. Make blood smears with blood from the lavender top tube using the Diff-Safe dispenser. Make two slides. Allow to air dry and place in blue slide mailer. Remove the Diff-Safe from the tube! Do not forget to ship the tube after using it for the hematology slides.NOTE: The best source of information in con rmation of hematology results is the blood smear slide prepared by you at the time of draw. Your diligence in slide preparation increases the opportunity to provide hematology results.


SM3 RNA1. Sample blood to be drawn into PAXgene tubes. Ensure the PAXgene Blood RNA tubes are at room

temperature (18C to 25C) prior to use, and labeled with the protocol number, subject number, subject initials and date and time of collection. The PAXgene Blood RNA tube should be the last tube drawn in the phlebotomy procedure.

2. Draw 2.5 ml of blood in each of the three PAXgene tubes. Hold the PAXgene tube vertically, below the donors arm, during blood collection. Allow at least 10 seconds for a complete blood draw to take place. Ensure that the blood ow has stopped owing into the tube before removing the tube from the holder. Gently invert the PAXgene Blood RNA tubes 8-10 times immediately after blood collection.

3. Store the PAXgene Blood RNA tube upright at room temperature for at least 2 hours.

4. Stand the PAXgene Blood RNA tubes upright in a wire rack and transfer to a 20C freezer until shipment. Do not freeze tubes upright in a Styrofoam tray as this may cause the tubes to crack. Ship samples on dry ice to to Covance CLS day of collection, if scheduling permits or the next day after processing.

Frozen

Day of collection

orNext

day after processing

Page: 22205263_TMEA






Shipping frequency


WHOLE BLOODDNA IsolationDraw whole blood samples last except when collecting coagulation at the same visit. One 10 mL lavender top tube with a red dot. Fill tube completely. Mix immediately by gently inverting the tube 10-15 times. Do Not centrifuge sample. Ship this blood sample for DNA analysis at ambient temperature the day of collection to Covance CLS.


BIOPSYSM5 Biopsy FormalinSee Endobronchial Biopsy Instructions in the Study Reference Manual supplied by Centocor.

To x the biopsies, go to your bulk supplies and pull 2 of the pre- lled formalin jars and 2 pre lled 70% ethanol 1.8 mL tubes. Fix each of the biopsies in fresh 10% neutral buffered formalin at room temperature for 4-6 hours.

Transfer the biopsy samples into 2 pre lled 70% ethanol 1.8 mL tubes

Use the barcode labels with the green bar labeled SM5 Biopsy Formalin, found in the kit to label the pre- lled ethanol tubes.

Ship these biopsies samples at ambient temperature after processing to Covance CLS day of collection, if scheduling permits or next day after processing.

Ambient

Day of collection or

Next day after

processing

SM6 Biopsy RNASee Endobronchial Biopsy Instructions in the Study Reference Manual supplied by Centocor.

Place the remaining 4 Endobronchial Biopsies into the four labeled 2 mL cryovials with the blue bar containing 1 mL of RNAlater labeled SM6 Biopsy RNA. Keep biopsy samples in RNAlater at room temperature for 2 hours and then freeze at -80C until shipment. Ship frozen on dry ice to Covance CLS day of collection, if scheduling permits or next day after processing.

Frozen

Day of collection or

Next day after

processing

Page: 23205263_TMEA






Shipping frequency


BIOPSYSM7 Bronchial BrushSee Bronchial Brushing Instructions in the Study Reference Manual supplied by Centocor.

Immediately place the cytobrush in the prepared pre-labeled 5 mL tube labeled SM7 Bronchial Brush and swirl vigorously for approximately 30 seconds to remove the cells from the brush. Discard brush. Repeat for 5 additional cytobrushes into the same cryovial.

Freeze immediately at -80C until shipment. Ship frozen on dry ice to Covance CLS day of collection.


NASAL BRUSH IN RNALATERSM13 Nasal BrushingProcedure:

Using the nasal speculum in the kit, epithelial cells will be collected from the right inferior turbinate with a standard cytology brush. No local anesthesia is necessary.

The nasal speculum is used to spread the naris while the standard cytology brush is inserted underneath the right inferior nasal turbinate. The brush is gently rotated in place for 3 s, removed, and immediately placed in 0.5 mL RNA later.

Submerge the brush tip ino the tube containing RNAlater, rotate brie y in the solution , then cut the handle of the brush, so the brush tip remains in the cryovial.

Brushing will be immediately placed in the RNAlater and then frozen at -70 C until shipment to Covance day of collection.


Page: 24205263_TMEA






Shipping frequency


SPUTUMSM8 Sputum Supernatant See Induced Sputum Collection Instructions in the Study Reference Manual supplied by Centocor

Aliquot the supernatant equally in to the ve 1.5 mL green Eppendorf tubes labeled SM8 Sputum Supernatant. Freeze immediately at -80C until shipment. Ship frozen on dry ice to Covance CLS day of collection.

Do not return to Covance

x5 Frozen Day of collection

SM9 Sputum CytospinSee Induced Sputum Collection Instructions in the Study Reference Manual supplied by Centocor

Air dry slides at least 10-15 minutes and then x the slides in the methanol for one minute. After air-drying, apply the barcode labels provided in the sputum kit, on the same side as the cells.

Place 1 slide in each mailer labeled SM9 Sputum Cytospin. Ship the slide(s) at ambient temperature after processing to Covance CLS.

Ambient After Processing

SM10 Sputum Cell Pellet (for mRNA)See Induced Sputum Collection Instructions in the Study Reference Manual supplied by Centocor

Place the Cell Pellet in to the 1.8 mL cryovial labeled SM10 Sputum Cell Pellet. Freeze immediately at -80C until shipment in. Ship frozen on dry ice to Covance CLS day of collection.


Page: 25205263_TMEA

2003 Covance CLS

SPECIMEN COLLECTION PROCEDURES FOR COAGULATION TESTING

English_Coagulation Testing_Update: 20111013

! Please make sure that all screw caps are tightly secured!

Blood Collection PrecautionsSpecial care is needed for collecting and handling blood samples intended for coagulation testing. If sample clotting or hemolysis occurs during collection or the aliquot is contaminated with platelets the test result will be cancelled.

Check the expiration date on all collection tubes. Do not use expired tubes for sample collection.

Coagulation results are impacted if the patient has a hematocrit of 55% or more. Please contact the Covance CLS investigator call center for instructions.

Blood specimens for coagulation testing are best obtained by venipuncture that collects the specimen directly into a tube containing citrate anticoagulant. Using a syringe, winged blood collection set (butterfly needle), or intra-vascular devices is not recommended, they risk hemolysis, clotting and/or dilution.

Note: Tube should be completely filled by the vacuum in order to obtain the correct ratio of blood to anticoagulant. Over or under filling alters the ratio and changes results. If the draw tube is less than 90% filled, the sample should be recollected.

Methods for Obtaining Blood Specimens for Coagulation TestingVenipuncture: If multiple collection tubes are being filled, draw the citrate tube last. If it is the only tube drawn, consider drawing a discard tube first. Mix the blood and additive thoroughly by gentle inversion 8 to 10 times.

Vascular access device: i.e. central line or an indwelling catheter. Withdraw and discard at least 2 mL of blood. Draw the citrate tube and immediately mix as above.

Prior to centrifugation gently rock the tube back and forth while examining the sample for visible clots, if so, please recollect the sample. Clots indicate consumption of coagulation factors and therefore removing the clots will not salvage the sample.1. Centrifuge the citrate tube within 30 minutes after draw. A centrifuge with a swing-out bucket rotor is

recommended. Do not refrigerate the blood prior to centrifugation.2. Centrifuge the citrate tube at 1500 to 2000 x g for 15 minutes (preferably 2000 x g). Using lower speeds for

longer times is not acceptable.3. Allow the centrifuge to stop without using the braking mechanism.4. Immediately remove the citrate tube from the centrifuge, taking care not to disturb the interface between the

plasma and the cells. Place the tube upright into a rack. Illuminate the side of the tube(s) in the rack in order to see the interface clearly. You may see a hazy layer above the blood cells, this contains WBC and platelets.

5. Carefully remove the tube stopper. Use a fresh Covance-supplied pipette to transfer the plasma into the appropriately labeled transport vial(s). Do not reuse a pipette from previous samples. Do NOT touch or aspirate the hazy layer. Label the transport tube with the patient identi cation (initials or patient ID number). If the plasma appears hemolyzed (red), do not submit the sample, please recollect it.

6. Secure the screw cap lid(s).7. Discard draw tube. Do NOT send back to Covance.8. Immediately place the citrate plasma aliquot into a -20C or -70C freezer. Ship the frozen plasma to Covance

on dry ice as directed in your protocol.

Page: 26205263_TMEA

2003 Covance CLS

SPECIMEN COLLECTION PROCEDURES FOR PAXgene BLOOD RNA

English_Collection Procedures PAXgene Blood RNA Tube_Update: 20100614

The PAXgene Blood RNA Tubes should be the last tubes drawn in the phlebotomy procedure.

NOTE: There are separate instructions for collecting PAXgene RNA samples and PAXgene DNA samples.

Please review the PAXgene Blood RNA Product Circular included in this manual. It is critical to review Section III (Specimen Collection and Preparation for Analysis) prior to PAXgene Blood RNA collection.

CAUTION: PAXgene Blood RNA tubes contain a chemical additive. It is important to avoid backflow from the tube to eliminate possible patient adverse reactions.

PAXgene Blood RNA Tube Collection Instructions NOTE: You must NOT draw blood directly from the needle into the PAXgene Blood RNA tube. You must NOT use a syringe to draw blood and then add it to the tube.

1) After prepping the venipuncture site with an antiseptic and applying a tourniquet, insert the butterfl y needle into the patients vein.

2) It is important that the PAXgene Blood RNA tube is at room temperature (18-25 C) prior to use.

3) Fill all required collection tubes, leaving the 2.5 mL PAXgene Blood RNA tube as the FINAL TUBE to be collected. If the PAXgene Blood RNA tube is the only tube required, collect blood into a 2 mL discard tube prior to collecting the PAXgene Blood RNA tube. The discard tube must be fi lled with at least 2 mL of blood to fl ush the air from the tubing.The following techniques shall be used to prevent possible backflow:a. Place donors arm in a downward position.b. Hold tube in a vertical position, below the donors arm during blood collection.c. Release tourniquet as soon as blood starts to fl ow into tube.d. Make sure tube additives do not touch stopper or end of the needle during venipuncture.

4) Ensure that blood has stopped fl owing into the PAXgene Blood RNA tube before removing the tube from the holder (at least 10 seconds).

5) Gently invert the PAXgene Blood RNA tube 8-10 times.6) Store and ship samples according to your protocol requirements.

WARNING: The contents of the PAXgene tube are irritating to the eyes, respiratory system and skin. Refer to the PAXgene Blood RNA Product Circular Section III (Warnings) in the event of an exposure.

Page: 27205263_TMEA

English_PAXgene Blood RNA Tube_Update: 20070411 2003 Covance CLS

Page: 28205263_TMEA

Page: 29205263_TMEA

Page: 30205263_TMEA

Page: 31205263_TMEA

English_Collection Procedures PAXgene Blood DNA Tube_Update: 20080701 2003 Covance CLS

SPECIMEN COLLECTION PROCEDURES FOR PAXgene BLOOD DNA

NOTE: There are separate instructions for collecting PAXgene DNA samples and PAXgene RNA samples.

Please review the PAXgene Blood DNA Product Circular included in this manual. It is critical to review Section V (Specimen Collection and Preparation for Analysis) and Section VIII (Prevention of Backflow) prior to PAXgene Blood DNA collection.

CAUTION: PAXgene Blood DNA tubes contain a chemical additive. It is important to avoid backflow from the tube to eliminate possible patient adverse reactions.

PAXgene Blood DNA Tube Collection InstructionsNOTE: You must NOT use a syringe to draw blood and then add it to the tube.

1) Ensure that the PAXgene Blood DNA tube is at room temperature (18-25C) prior to use and properly labelled with patient identi cation.

2) The PAXgene Blood DNA tube should be the last tube drawn.

3) Collect blood into the PAXgene Blood DNA tube using your institutions recommended procedure for standard venipuncture technique. (See Prevention of Back ow Section)a) Place donors arm in a downward position.b) Hold tube with the stopper uppermost.c) Release tourniquet as soon as blood starts to ow into tube.d) Make sure tube additives do not touch stopper or end of the needle during venipuncture.

4) Ensure that the blood has stopped owing into the tube before removing the tube from the holder.5) After blood collection, gently invert the PAXgene Blood DNA tube 8 - 10 times.6) Store and ship samples according to your protocol requirements.

WARNING: The contents of the PAXgene tube are irritating to the eyes, respiratory system and skin. Refer to the PAXgene Blood DNA Product Circular Section IV (Warnings) in the event of an exposure.

Page: 32205263_TMEA

A QIAGEN / BD COMPANY

Product Circular

To be used only in conjunction with thePAXgene Blood DNA Kit (Cat. No. 761133) or the

PAXgene Blood DNA Validation Kit (Cat. No. 761132)

*Included in PAXgene Blood DNAValidation Kit (Cat. No. 761132)

PAXgene Blood DNA TubeFOR THE COLLECTION OF WHOLE BLOOD

FOR GENOMIC DNA ISOLATION

For Research Use OnlyNot for use in diagnostic procedures

Catalog No. 761115 NA

Catalog No. 761125 Ex NA

Catalog No. 769989*

Page: 33205263_TMEA

1I. Introduction

The PAXgene Blood DNA Tube is a plastic, evacuated tube, for the collectionof whole blood for the isolation of genomic DNA. The use of this tube isrestricted to research use only, and therefore the use of this product fordiagnostic procedures and patient management is strictly prohibited. Neitherthe clinical utility nor the performance characteristics of the PAXgene BloodDNA Tube and Kit as part of an in vitro diagnostic procedure have beenestablished. Its suggested use is for molecular test methods that require intactgenomic DNA from whole blood. These test methods include, but are notlimited to, PCR (polymerase chain reaction) and Southern blot analysis.

Product Summary

Sterile8.5 mL Draw Volume16x100 mm Plastic Tube with BD Hemogard Closure2.0 mL DNA additive100 Tubes/boxFor Research Use Only. Not For Use In Diagnostic Procedures.

II. Summary and Explanation

Research applications, including pharmacogenomic studies, gene expressionstudies, and SNP genotyping, yield important data. Therefore, the use ofstandardized methods for sample collection and nucleic acid isolation are ofincreasing importance. The PAXgene Blood DNA System provides an efficientmethod for standardized blood collection, transport and storage of wholeblood specimens and isolation of their genomic DNA. High yields of pure DNAare obtained that perform well in a wide range of downstream researchapplications.

III. Principle of Procedure

The PAXgene Blood DNA Tube provides a means for the collection of wholeblood for the isolation of genomic DNA in a closed, evacuated system. Blood iscollected under a standard phlebotomy protocol into an evacuated tube thatcontains 2.0 mL of DNA additive. It yields a ratio of .24 mL of DNA additiveper/mL of blood when the evacuated tube is filled correctly to its 8.5mL-drawvolume. Complete isolation of genomic DNA is carried out using the PAXgeneBlood DNA Kit (Catalog no. 761133) or the PAXgene Blood DNA Validation Kit(Catalog No. 761132).

Page: 34205263_TMEA

2IV. Warnings

Contents of this tube may cause irritation to eyes, respiratory system andskin. After inhalation, supply fresh air, and seek medical advice in case of

complaints. After skin contact, immediately wash with water and soap and rinse

thoroughly. After eye contact, rinse immediately with plenty of water for at least 15

minutes and seek medical advice. After swallowing, immediately seek medical advice.

V. Specimen Collection and Preparation For Analysis

A. Required Blood Collection Accessories. (Not included with PAXgene System)

1. Needle or blood collection set, such as the BD Vacutainer Needle orBD Vacutainer Blood Collection Set. (See "Ordering Information" forexample.)

2. A BD Vacutainer needle holder must be used to ensure proper function.(See "Ordering Information" for example.)

3. Labels for positive donor identification of samples.4. Alcohol swab for cleansing site.5. Dry sterile gauze.6. Tourniquet.7. Needle disposal container for used needle or needle/holder combination.

B. Procedure for Specimen Collection

1. Ensure that the PAXgene Blood DNA Tube is at room temperature (18-25C)prior to use and properly labeled with patient identification.

2. The PAXgene Blood DNA Tube should be the last tube drawn.3. Collect blood into the PAXgene Blood DNA Tube using your institution's

recommended procedure for standard venipuncturetechnique. (See Prevention of Backflow Section)

4. Ensure that the blood has stopped flowing into the tube before removingthe tube from the holder.

5. After blood collection, gently invert the PAXgene Blood DNA Tube 8 - 10times.

10

Page: 35205263_TMEA

36. Store the PAXgene Blood DNA Tube upright at room temperature (18-25C),4C, -20C, or -70C.

C. Procedure for Specimen Preparation for Analysis

Blood samples should be processed in accordance with the instructions providedwith the PAXgene Blood DNA Kit (Cat. No. 761133) or the PAXgene Blood DNAValidation Kit (Cat. No. 761132).

VI. Limitations of System

1. The use of this tube is restricted to research use only, and therefore the useof this product for diagnostic procedures and patient management is strictlyprohibited. Neither the clinical utility nor the performance characteristics ofthe PAXgene Blood DNA Tube and Kit as part of an in vitro diagnosticprocedure have been established.

2. The quantity of blood drawn varies with altitude, ambient temperature,barometric pressure, tube age, venous pressure, and filling technique.

3. Blood samples obtained with the PAXgene Blood DNA Tube should beprepared only with the PAXgene Blood DNA Kit (Cat. No. 761133) or thePAXgene Blood DNA Validation Kit (Cat. No. 761132).

4. Under-filling of tubes will result in an incorrect blood-to-additive ratio andmay lead to incorrect analytical results or poor product performance.

VII. Precautions

1. Practice Universal Precautions. Use gloves, gowns, eye protection, otherpersonal protective equipment, and engineering controls to protect fromblood splatter, blood leakage, and potential exposure to blood bornepathogens.

2. Handle all biologic samples and blood collection "sharps" (lancets, needles,luer adapters, and blood collection sets) according to the policies andprocedures of your facility. Obtain appropriate medical attention in theevent of any exposure to biologic samples (for example, through a punctureinjury), since they may transmit viral hepatitis, HIV (AIDS), or other infectiousdiseases. Utilize any built-in used needle protector, if the blood collectiondevice provides one. PreAnalytiX does not recommend reshielding usedneedles. However, the policies and procedures of your facility may differ andmust always be followed.

3. Discard all blood collection tubes in biohazard containers approved for theirdisposal.

4. Do not re-use PAXgene Blood DNA Tubes.5. Do not use PAXgene Blood DNA Tubes after expiration date printed on the

tube label.

Page: 36205263_TMEA

46. Since this PAXgene Blood DNA Tube contains a chemical additive,precautions should be taken to prevent possible backflow from the tubeduring blood drawing (See "Prevention of Backflow" section).

7. The PAXgene Blood DNA Tube should be the last tube drawn in thephlebotomy process.

8. Excessive centrifugation speed (over 10,000 RCF) may cause PAXgene BloodDNA Tube breakage, exposure to blood and possible injury.

9. Transferring a sample from a syringe to a tube is not recommended.Additional manipulation of sharps increases the potential for needlestickinjury. In addition, depressing the syringe plunger during transfer cancreate a positive pressure, forcefully displacing the stopper and sample andcausing a potential blood exposure. Using a syringe for blood transfer mayalso cause over or under filling of tubes, resulting in an incorrect blood-to-additive ratio and potentially incorrect analytical results.

10. The use of the PAXgene Blood DNA Tube is contraindicated with anintravenous (I.V.) line. This is critical to avoid erroneous laboratory datafrom I.V. fluid contamination.

VIII. Prevention of Backflow

Since PAXgene Blood DNA Tubes contain a chemical additive, it is important toavoid possible backflow from the tube, with the possibility of adverse donorreactions. To guard against backflow, observe the following precautions:

1. Place donor's arm in a downward position.2. Hold tube with the stopper uppermost.3. Release tourniquet as soon as blood starts to flow into tube.4. Make sure tube additives do not touch stopper or end of the needle during

venipuncture.

IX. Storage

Store the PAXgene Blood DNA tubes at room temperature (18-25C). Do notuse tubes after their expiration date.

X. Instructions for Removal of BD Hemogard Closure

1. Grasp the PAXgene Blood DNA Tube with one hand, placing the thumbunder the BD Hemogard Closure. (For added stability, place arm on solidsurface.) With the other hand, twist the BD Hemogard Closure whilesimultaneously pushing up with the thumb of the other hand ONLY UNTILTHE TUBE STOPPER IS LOOSENED.

2. Move thumb away before lifting closure. DO NOT use thumb to pushclosure off tube. Caution: If the tube contains blood, an exposure hazardexists. To help prevent injury during closure removal, it is important that

Page: 37205263_TMEA

5the thumb used to push upward on the closure be removed from contactwith the tube as soon as the BD Hemogard Closure is loosened.

3. Lift closure off tube. In the unlikely event of the plastic shield separatingfrom the rubber stopper, DO NOT REASSEMBLE CLOSURE. Carefully removerubber stopper from tube.

XI. Instructions For Reinsertion of BD Hemogard Closure

1. Replace closure over tube.2. Twist and push down firmly until stopper is fully reseated. Complete

reinsertion of the stopper is necessary for the closure to remain securely onthe tube during handling.

TECHNICAL ASSISTANCEIf you have any questions regarding the PAXgene Blood DNA System, contact one of theQIAGEN Technical Services Departments listed on page 7.

ANALYTIC EQUIVALENCY

Whenever changing any manufacturer's blood collection tube type or size for a particularlaboratory assay, the Laboratory Director should review the tube manufacturer's dataand/or previous data generated to establish/verify your reference range data for yourspecific instrument and reagent system. Based on such information, the laboratory canthen decide if changes are indicated.

PAXgene is a trademark of PreAnalytiX GmbH.

BD, Vacutainer, Hemogard, and Safety-Lok are trademarksof Becton, Dickinson and Company.U. S. Patent Nos. 4,741,446 and 4,991,104Becton, Dickinson and CompanyFranklin Lakes, NJ 07417-1885

Manufactured for PreAnalytiX GmbH (Hombrechtikon, CH) by BD (Plymouth, UK)Distributed for PreAnalytiX GmbH by QIAGEN2003 PreAnalytiX GmbH.

www.PreAnalytiX.com

Page: 38205263_TMEA

English_Blood Smear Preparation 1/2_Update: 20041022 2003 Covance CLS

BLOOD SMEAR PREPARATION

1. Write appropriate identi ers on the frosted end of both hematology slides using a pencil.

2. After mixing the hematology tube, insert the Diff-Safe dispenser into the rubber stopper.

3. Turn the tube upside down and press the Diff-Safe dispenser against the slide, 0.5 cm from the frosted end. Discontinue pressure the instant the drop appears.

4. Holding the second slide at a 30 angle, pull the slide towards the drop of blood until contact is made.

! Remove the Diff-Safe dispenser and discard it in an approved medical waste container. Do not forget to ship the tube with the hematology slides!

5. Allow the droplet to draw completely across the edge of the slide. Gently push the second slide forward (only allowing the weight of the slide to be applied on the glass surface).

6. Repeat the process for the other slide. Allow the slides to air dry thoroughly while lying at. Return slides to plastic mailer(s) for shipment.

Page: 39205263_TMEA

English_Blood Smear Preparation 2/2_Update: 20090615 2003 Covance CLS

BLOOD SMEAR PREPARATION AND DIFF-SAFE SAFETY TIPS

BLOOD SMEARS

Examples of well-made slides Examples of incorrect slides! !

DIFF-SAFEIMPORTANT: Instructions for Use

After the blood smear preparation, please REMOVE the Diff-Safe from the tube.

Place tube into the specimen collection bag WITHOUT the Diff-Safe.

If the Diff-Safe is not removed properly, the blood will spill into the specimen collection bag, and the samples will be useless.

! Please remove the Diff-Safe from the tube!

Page: 40205263_TMEA

2003 Covance CLS

SINGLE USE NEEDLE PROTECTION DEVICE INSTRUCTIONS

English_Venipuncture Needle Protection Device_Update: 20050310

INSTRUCTIONS FOR USE:

b

Holding both pink shield and green cap, twist and remove white cap.

While holding the needle firmly, screw holder onto needle until it fits securely.

a) Rotate pink safety shield back toward the holder.b) Twist and pull green needle cap straight off.

Perform venipuncture according to your facilitys established procedures.

Immediately after removing needle from vein, cover needle by pushing pink safety shield forward with thumb until an audible click is heard. DO NOT attempt to engage shield by pressing against hard surface.

DO NOT remove needle from holder. Dispose of the needle and holder as one unit into nearest sharps container. DO NOT REUSE.

IMPORTANT SAFETY TIPS DO NOT REUSE HOLDER Holder threads are designed to be used ONLY ONCE. Reuse of holder is

potentially unsafe and could result in serious injury or exposure to bloodborne pathogens.

Once holder has been attached to the needle, DO NOT UNWIND it to readjust, or to change needles.

Dispose of needle and holder as a single unit.

BD Vacutainer SystemsPreanalytical Solutions1 Becton DriveFranklin Lakes, NJ 07417

BD, BD Logo and Eclipse are trademarks of Becton, Dickinson and Company. 2002 BD.

Page: 41205263_TMEA

English_Adaptation Procedure for Vacutainer and Monovette_Update: 20101104 2010 Covance CLS

PROCEDURE FOR SARSTEDT MONOVETTE DRAWING SYSTEM

Monovette TubeItems needed to perform blood draw using a butterfly needle and Monovette Tube

Butterfly assembly with multi-adapter

Monovette tube

1. Insert the tip of the tube into the multi-adapter and twist to lock. (See below for Blood draw technique

options)

x To draw blood using aspiration technique (syringe-like): Insert the Monovette draw tube into the open end of the multi-adapter and lock it into place with a clockwise twist. Insert the needle into the vein and pull back on the plunger until it rmly locks into the base of the tube, lling that tube. Twist counterclockwise to disconnect the tube from the multi-adapter and connect another tube in the same way, if required. After lling tubes, break off the plunger(s) when all draws are completed.

x To use vacuum technique (Vacutainer-like): Pull back on the plunger of the Monovette tube until it rmly locks into the base of the tube, thus creating a vacuum. If drawing multiple Monovette tubes, prepare them in advance of the venipuncture in the same way. Break off the plunger(s). Insert the needle into the vein and then insert the Monovette tube into the open end of the multi-adapter, twisting clockwise to secure the connection. The vacuum that you created draws the blood into the tube. Twist counterclockwise to disconnect the lled tube. Insert the next tube with the prepared vacuum, if required.

Vacutainer TubeFor some blood draws, there is no Monovette tube equivalent to the Vacutainer tube. Following the instructions given below, you can adapt a Vacutainer tube on a Monovette drawing system.Items needed to perform blood draw using a butterfly needle and Vacutainer Tube

Butterfly assembly with multi-adapter

Vacutainer Holder Vacutainer Tube

1. Remove multi-adapter from butter y assembly

2. Screw the needle of the butter y assembly into the vacutainer holder

3. Insert Vacutainer tube into holder, blood will ow into the tube until the vacuum is lled.

Page: 42205263_TMEA

English_Specimen Collection Procedure for Urine Pregnancy Test_Update: 20071008 2003 Covance CLS

SPECIMEN COLLECTION PROCEDURES FOR URINE PREGNANCY TEST

Collection Instructions:1. Collect urine in a clean container (urine may be collected anytime during the day but for optimal

results, use the rst urine voided in the morning because the concentration of hCG is greatest at this time.) Samples may be stored 72 hours refrigerated (36-46F, 2-8C) prior to testing. If the specimen has been refrigerated, it must be brought to room temperature before testing.

2. Remove the test device from the pouch and place it on a at surface. 3. Dispense 4 drops of urine into the round sample well. Wait for the colored lines to appear. 4. Read results after 4 minutes and no later than 30 minutes.

Reading the results: 1. Positive Result - the test is positive if one colored line appears in the T (test) window and one colored

line appears in the C (control) window. Any colored line in the T window should be considered positive. 2. Negative Result - the test is negative if a colored line appears only in the C (control) window. 3. Invalid Result - the test is invalid if no color appears in the C (control) window even if a colored

line appears in the T (test) window. If no colored line appears in the C (control) window, add 1 or 2 additional drops of urine and wait an additional 4 minutes. If a colored line still does not appear in the C (control) window, the test is invalid and should be repeated using another test kit.

Quality Control Each test device includes a built-in control for the procedure. Correct procedural technique is confirmed when a colored line appears in the C (control) window. With each shipment of a new kit lot number Covance runs an external control. Covance will not reimburse the purchase of external controls.

Lot number and expiration date

Page: 43205263_TMEA

2003 Covance CLS

INSTRUCTIONS FOR COMPLETING REQUISITION FORMS

English_Instructions for Completing Requisition Forms_Update: 20100512

# Please complete all the required information with a black ball point pen. This information is required for patient identifi cation and result reporting. !

Any errors or missing details with regard to patient demographics will cause a delay in the reporting of the results until information is verifi ed!

Send the white copy of the completed requisition form together with the relevant samples to Covance Central Laboratory Services

Page 1 of 1

B

ar_

req

Covance Central Laboratory Services S.A. Rue Mose-Marcinhes 7 1217 Meyrin Geneva Switzerland Tel: +41-(0)-58-822-7000 Investigators: +41-(0)-58-822-7900

Requisition_n Accession No. THE ACCESSION NUMBER IS

THE REFERENCE NUMBER FOR COMMUNICATION WITH COVANCE.

Bar_req

Covance internal use ONLYLabel_6

Bar_req

B

ar_

req

Covance internal

useONLY

Employee Visa

Tube Count

Ambient=

Frozen=

Refrigerated=

Slides=

Validation

Investigator : Inv_n Address_1Address_2Address_3Address_4Address_5Address_6Address_7

Laboratory Requisition Form PHARMACEUTICAL COMPANY Protocol: ABCD.123.EF

x-part

XX XXXXXX XXXXXX1

Patient Initials(If no middle initial, a dash will be

used)

First Middle Family/Last

COMPLETE ALL BOXES IN THIS SECTION WITH BLACK BALL POINT PEN. FAILURE TO COMPLETE ALL BOXES WILL DELAY REPORTS.

VISIT: NAME

Patient Number

Origin1=Caucasian 4=Native American

2=Black 5=Asian/Oriental3=Hispanic 99=Other

BirthdateComplete month field in English

(Example: 02 JUN 1968)

Day Month Year

24 Hour Clock

:Collection Time(Record Midnight as 23:59)

Requisition Completed byFull name in capital letters

Samples Collected byFull name in capital letters

Collection DateComplete month field in English

(Example: 01 JAN 2001)

Day Month Year

Phone numberOf the person completing the

requisition

OPTIONAL TESTING refer to following page(s) or below for collection and shipping instructions

Please check the box(es) to ensure proper ordering of optional test(s)! If you fail to mark the checkbox, testing may be ordered per Covance policy without investigator notification.

Test name Test name

REQUIRED TESTING refer to following page(s) or below for collection and shipping instructions

Sex Male Female

YES NO N/A Is patient a female of childbearing potential? (Check one box - mandatory) If answer is YES, the Serum Beta hCG, Qualitative will be automatically performed. No additional serum required.

Patient weight: (Mandatory for Creatinine Clearance calculation) kg

WHITE COPY-COVANCE YELLOW COPY-INVESTIGATOR PINK COPY-INVESTIGATOR PLEASE DO NOT RETURN EMPTY CONTAINERS TO COVANCE.

Visit 1 (PVC=1)Visit 2 Visit 3

VISIT:Check one box

AUTHORIZATION IS REQUIRED FOR ADDITIONAL TESTINGComments:

1. Patient Number

Visit (if applicable)

1. Patient Initials (if applicable)

2. Birthdate

2. Sex (Check appropriate box)

Origin (if applicable)

3 Specimen Collection Date

3. Specimen Collection Time

Name of the person collecting the samples/Name and phone number of the person completing the requisition

Check the appropriate box (if applicable to your site).

Write in appropriate number (if applicable to your site)

1. Information required for patient identifi cation.2. Information required in order to provide age and gender for specifi c reference ranges3. Information required to calculate specimen stability.

Optional Testing. Check Appropriate box (if applicable)

Write your comments here

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Requisition_n

Accession No.

THE ACCESSION NUMBER IS THE REFERENCE NUMBER FOR COMMUNICATION WITH COVANCE.

Bar_req

Covance internal use ONLY

Label_6 Bar_req

B

ar_

req

Covance internal

use ONLY

Employee Visa

Tube Count

Ambient=

Frozen=

Refrigerated=

Slides=

Validation

Investigator : Inv_n Address_1 Address_2 Address_3 Address_4 Address_5 Address_6 Address_7

Laboratory Requisition Form Janssen Research & Development, LLC. Protocol: NOCOMPOUNDASH0001

3-part

DC 130204

205263

1

Subject Initials (If no middle initial, a dash will be

used)



VISIT: SCREEN HEALTHY

Subject Number 0

Birthdate Complete month field in English


Day Month Year

24 Hour Clock

: Collection Time

(Record Midnight as 23:59)

Requisition Completed by Full name in capital letters

Samples Collected by Full name in capital letters

Collection Date Complete month field in English


Day Month Year

Phone number Of the person completing the

requisition


Sex

Male Female

WHITE COPY-COVANCE YELLOW COPY-SEND WITH FROZEN SHIPMENTS PINK COPY-INVESTIGATOR PLEASE DO NOT RETURN EMPTY CONTAINERS TO COVANCE.

ADDITIONAL TESTING IS NOT ALLOWED Comments:

For all Females perform a urine pregnancy test. (Pull from bulk supplies)

For all subjects perform an alcohol breath test. (Pull from bulk supplies)

Be sure to pull a Sputum kit

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Label_6

Bar_req

B

ar_

req


Requisition_n

Accession No.


Bar_req

3-part

RMK 100712

205263

1

THE FOLLOWING REQUIRED SPECIMENS MUST BE SHIPPED AMBIENT DAY OF COLLECTION:

Hematology & Differential Panel Draw whole blood samples last except when collecting coagulation group at the same visit. One 2 mL lavender top tube. Fill tube completely. Mix immediately by gently inverting the tube at least 8 to 10 times. Make blood smears with blood from the lavender top tube using the Diff-Safe dispenser. Make two slides. Allow to air dry and place in blue slide mailer. Remove the Diff-Safe from the tube! Do not forget to ship the tube after using it for the hematology slides. NOTE: The best source of information in confirmation of hematology results is the blood smear slide prepared by you at the time of draw. Your diligence in slide preparation increases the opportunity to provide hematology results. Urine Macro Panel One 10 mL orange top urine tube with preservative tablet. Transfer specimen from standard urine collection cup into tube labeled URINALYSIS. Do not fill above 9 mL mark. Screw cap on tightly. HIV-1/HIV-2 Antibody One 2.5 mL gold top serum separation tube. Fill tube completely. It is important to thoroughly mix the blood with the clotting activation agent by inverting the tube not less than five times. Allow blood to clot for 30 minutes (tube standing upright). Centrifuge at 1500 to 2000 x g for 15 minutes until clot and serum are separated by a well-formed polymer barrier. Use pipette provided to transfer all the serum into the 5 mL plastic vial labeled HIV-1/HIV-2. Hepatitis Panel One 2.5 mL gold top serum separation tube. Fill tube completely. It is important to thoroughly mix the blood with the clotting activation agent by inverting the tube not less than five times. Allow blood to clot for 30 minutes (tube standing upright). Centrifuge at 1500 to 2000 x g for 15 minutes until clot and serum are separated by a well-formed polymer barrier. Use pipette provided to transfer all the serum into the 5 mL plastic vial labeled HEPATITIS. Comprehensive Drug Screen One 30 mL urine tube without preservative tablet. Transfer specimen from standard urine collection cup into tube labeled URINE DRUG SCREEN. Do not fill above 30 mL mark. Screw cap on tightly. THE FOLLOWING REQUIRED SPECIMENS MUST BE SHIPPED AS INDICATED DAY OF COLLECTION:

Chemistry Panel CKMB Troponin I One 5 mL gold top serum separation tube. Fill tube completely. It is important to thoroughly mix the blood with the clotting activation agent by inverting the tube not less than five times. Allow blood to clot for 30 minutes (tube standing upright). Centrifuge at 1500 to 2000 x g for 15 minutes until clot and serum are separated by a well-formed polymer barrier. Use pipette provided to transfer all the serum equally into the three 5 mL plastic vials labeled CHEMISTRY (ship ambient, day of collection), CK-MB FROZEN, and TROPONIN I FROZEN (freeze immediately at -20C until shipment; ship frozen on dry ice, day of collection).

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Label_6

Bar_req

B

ar_

req


Requisition_n

Accession No.


Bar_req

3-part

RMK 100614

205263

1

THE FOLLOWING REQUIRED SPECIMENS MUST BE SHIPPED FROZEN ON DRY ICE DAY OF COLLECTION:

Coagulation Panel Draw this tube last. One 1.8 mL blue top sodium citrate tube. Fill tube completely. Mix immediately by gently inverting the tube at least 8 to 10 times. Centrifuge at 1500 to 2000 x g for 15 minutes until cells and plasma are well separated. Use pipette provided to transfer all the plasma into the 3 mL plastic vial labeled COAGULATION PANEL FROZEN. Freeze immediately at -20C or -70C until shipment. Phadiatop One 2.5 mL gold top serum separation tube. Fill tube completely. It is important to thoroughly mix the blood with the clotting activation agent by inverting the tube not less than five times. Allow blood to clot for 30 minutes (tube standing upright). Centrifuge at 1500 to 2000 x g for 15 minutes until clot and serum are separated by a well-formed polymer barrier. Use pipette provided to transfer all the serum into the 5 mL plastic vial labeled PHADIATOP FROZEN. Freeze immediately at -20C until shipment. Cotinine, Urine One 10 mL yellow top urine tube without preservative. Transfer specimen from standard urine collection cup into tube labeled COTININE, URINE FROZEN. Do not fill above 9 mL mark. Screw cap on tightly. Freeze immediately at 20C until shipment.

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B

ar_

req


Requisition_n

Accession No.


Bar_req


Label_6 Bar_req

B

ar_

req

Covance internal

use ONLY

Employee Visa

Tube Count

Ambient=

Frozen=

Refrigerated=

Slides=

Validation



3-part

DC 130204

205263

2


used)



VISIT: BASELINE HEALTHY

Subject Number 0



Day Month Year

24 Hour Clock

: Collection Time






Day Month Year


requisition


Sex

Male Female




If consent for DNA testing is received pull separate DNA kit.


Collection Date dd-mmm-yyyy

Collection Time 24 hour format

PD Urine :

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Label_6

Bar_req

B

ar_

req


Requisition_n

Accession No.


Bar_req

3-part

DGF 110216

205263

2

THE FOLLOWING REQUIRED SPECIMENS MUST BE SHIPPED FROZEN ON DRY ICE AS INDICATED BELOW:

SM1 PD Serum One 8.5 mL gold top serum separation tube. Fill tube completely. It is important to thoroughly mix the blood with the clotting activation agent by gently inverting the tube no less than five times. Allow blood to clot for 30 minutes (tube standing upright). Centrifuge blood samples at room temperature within 1 hour of collection (minimum of 1500 x g for 15-20 minutes) until clot and serum are well separated. Use pipette(s) provided to transfer all of the separated serum (use 1 new pipette per sample) into the appropriately labeled cryotube vials. Distribute serum equally into all cryotube vials provided for the individual blood sample. Freeze as soon as possible at approximately -20C or lower until shipment in a non-automatically defrosting freezer. Do not exceed 30 minutes for the time between centrifuging the blood and freezing the serum. Ship frozen on dry ice to Covance CLS day of collection. SM2 PD Urine See Urine Collection Instructions in the Study Reference Manual supplied by Centocor. Transfer 1 mL of urine from sterile urine collection cup into the four appropriately labeled 1.8 mL, cryovials with the yellow bar, labeled SM2 PD Urine and into the 2 mL amber cryovial prefilled with BHT. Secure screw cap on tightly. Freeze immediately at -80C until shipment. Ship frozen on dry ice to Covance CLS day of collection. SM3 RNA 1. Sample blood to be drawn into PAXgene tubes. Ensure the PAXgene Blood RNA tubes are at room temperature (18C to 25C) prior to use, and labeled with the protocol number, subject number, subject initials and date and time of collection. The PAXgene Blood RNA tube should be the last tube drawn in the phlebotomy procedure. 2. Draw 2.5 ml of blood in each of the three PAXgene tubes. Hold the PAXgene tube vertically, below the donors arm, during blood collection. Allow at least 10 seconds for a complete blood draw to take place. Ensure that the blood flow has stopped flowing into the tube before removing the tube from the holder. Gently invert the PAXgene Blood RNA tubes 8-10 times immediately after blood collection. 3. Store the PAXgene Blood RNA tube upright at room temperature for at least 2 hours. 4. Stand the PAXgene Blood RNA tubes upright in a wire rack and transfer to a 20C freezer until shipment. Do not freeze tubes upright in a Styrofoam tray as this may cause the tubes to crack. Ship samples on dry ice to to Covance CLS day of collection, if scheduling permits or the next day after processing.

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B

ar_

req


Requisition_n

Accession No.


Bar_req


Label_6 Bar_req

B

ar_

req

Covance internal

use ONLY

Employee Visa

Tube Count

Ambient=

Frozen=

Refrigerated=

Slides=

Validation



3-part

DC 130204

205263

3


used)



VISIT: BRONCHOSCOPY HEALTHY

Subject Number 0

24 Hour Clock

: Collection Time






Day Month Year


requisition




Process SM6 Biopsy RNA prior to SM5 Biopsy Formalin



Collection Date dd-mmm-yyyy

Collection Time 24 hour format

PD Urine :

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Label_6

Bar_req

B

ar_

req


Requisition_n

Accession No.


Bar_req

3-part

MR 110323

205263

3

THE FOLLOWING REQUIRED SPECIMENS MUST BE SHIPPED AMBIENT AS INDICATED BELOW:

SM5 Biopsy Formalin See Endobronchial Biopsy Instructions in the Study Reference Manual supplied by Centocor. To fix the biopsies, go to your bulk supplies and pull 2 of the pre-filled formalin jars and 2 prefilled 70% ethanol 1.8 mL tubes. Fix each of the biopsies in fresh 10% neutral buffered formalin at room temperature for 4-6 hours. Transfer the biopsy samples into 2 prefilled 70% ethanol 1.8 mL tubes Use the barcode labels with the green bar labeled SM5 Biopsy Formalin, found in the kit to label the pre-filled ethanol tubes. Ship these biopsies samples at ambient temperature after processing to Covance CLS day of collection, if scheduling permits or next day after processing. THE FOLLOWING REQUIRED SPECIMENS MUST BE SHIPPED FROZEN ON DRY ICE AS INDICATED BELOW:

SM1 PD Serum One 8.5 mL gold top serum separation tube. Fill tube completely. It is important to thoroughly mix the blood with the clotting activation agent by gently inverting the tube no less than five times. Allow blood to clot for 30 minutes (tube standing upright). Centrifuge blood samples at room temperature within 1 hour of collection (minimum of 1500 x g for 15-20 minutes) until clot and serum are well separated. Use pipette(s) provided to transfer all of the separated serum (use 1 new pipette per sample) into the appropriately labeled cryotube vials. Distribute serum equally into all cryotube vials provided for the individual blood sample. Freeze as soon as possible at approximately -20C or lower until shipment in a non-automatically defrosting freezer. Do not exceed 30 minutes for the time between centrifuging the blood and freezing the serum. Ship frozen on dry ice to Covance CLS day of collection. SM2 PD Urine See Urine Collection Instructions in the Study Reference Manual supplied by Centocor. Transfer 1 mL of urine from sterile urine collection cup into the four appropriately labeled 1.8 mL, cryovials with the yellow bar, labeled SM2 PD Urine and into the 2 mL amber cryovial prefilled with BHT. Secure screw cap on tightly. Freeze immediately at -80C until shipment. Ship frozen on dry ice to Covance CLS day of collection. SM6 Biopsy RNA See Endobronchial Biopsy Instructions in the Study Reference Manual supplied by Centocor. Place the remaining 4 Endobronchial Biopsies into the four labeled 2 mL cryovials with the blue bar containing 1 mL of RNAlater labeled SM6 Biopsy RNA. Keep biopsy samples in RNAlater at room temperature for 2 hours and then freeze at -80C until shipment. Ship frozen on dry ice to Covance CLS day of collection, if scheduling permits or next day after processing. SM7 Bronchial Brush See Bronchial Brushing Instructions in the Study Reference Manual supplied by Centocor. Immediately place the cytobrush in the prepared pre-labeled 5 mL tube labeled SM7 Bronchial Brush and swirl vigorously for approximately 30 seconds to remove the cells from the brush. Discard brush. Repeat for 5 additional cytobrushes into the same cryovial. Freeze immediately at -80C until shipment. Ship frozen on dry ice to Covance CLS day of collection.

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B

ar_

req


Requisition_n

Accession No.


Bar_req


Label_6 Bar_req

B

ar_

req

Covance internal

use ONLY

Employee Visa

Tube Count

Ambient=

Frozen=

Refrigerated=

Slides=

Validation



3-part

DC 130204

205263

4


used)



VISIT: SCREEN ASTHMATIC

Subject Number 0



Day Month Year

24 Hour Clock

: Collection Time






Day Month Year


requisition


Sex

Male Female




For all subjects perform an alcohol breath t

nocompoundash0001 covance investigatormanual_eu_revised_04 feb 2013

Documents

collection kit

kit expiration dates

correct kit

kit box

glossary section

covance internal changes

covance clskit information

covance standard pages