1. Genentech, Inc. Protocol GO27912 Covance Central Laboratory Procedures November 2011
This document contains confidential and proprietary information and is the exclusive property of Covance Central Laboratory Services Inc. The reproduction, distribution, modification, performance or other use of this document, or any of the information contained herein, in whole or in part, without the express written consent of Covance Central Laboratory Services Inc, is prohibited. 1

2. Presentation Training Objectives
Ensure you understand the steps needed to ensure subject safety and increase the likelihood of having evaluable subjects at the end of the study
Ensure your site has the collection kits and supplies needed throughout the study
Use the collection kits according to protocol and visit schedule
Ensure properly completed requisition forms so that specimens can be processed without delay
Collect samples according to protocol requirements and accepted medical practices
Optimize subject safety by minimizing test cancellations or missed visits
Pack and ship specimens according to the procedures associated with your region and the needs of your study
Contact Covance to order additional supplies or learn the answers to questions you might have

3. Central Laboratory Topics
This presentation provides specific details about:
Supplies provided by Covance CLS
Collection kit use and inventory management
Requisition completion
Specimen collection and packaging
Courier arrangements
Contacting Covance CLS

4. Covance Central Laboratory Services
Location
Est.
Indianapolis, Indiana, USA
1986
Geneva, Switzerland
1992
Singapore
2000
Shanghai, China
2007
Kawagoe City, Japan
2010
Devoted exclusively to clinical trials
Combinable data
Global capabilities 4

5. Supplies Provided By Covance CLS

6. First Covance CLS Communication
Confirm site contact information
Correct mistakes and enter any missing information
Fax completed form to Covance CLS within 48 hours
Ensures:
Study supplies shipped to appropriate location
addresses used only for study related issues
e.g., reminders of upcoming holidays

7. Visit-specific collection kits
Initial Supplies (1/4)
Visit-specific collection kits
To obtain the highest quality specimens possible, store collection supplies at the recommended +4°C to 25°C (+39°F to 77°F)
Expired kits or kits/supplies in excess at end of study must be destroyed at site, do not return to Covance CLS
Visit
Screen,
CTC/CAP,
Arm C/D Urine DNA
C1D1,
C1D8
Unscheduled
# Kits
3 kits each
2 kits each
1 kit 7

8. Initial Supplies (2/4) Shipping supplies Shipping boxes
Ambient and frozen for shipments to Covance
Insulated ambient for shipments to Genentech
CTC samples
Site specific shipping documents
Air waybills, UPS shipping labels, Commercial Invoices, return address labels
Supplied in envelopes designated by shipping condition 8

9. Initial Supplies (3/4) Quick Reference Guide Generic
Provided in most local languages
Kit information tips
Requisition completion tips
Resupply
Inventory control tips 9

10. Initial Supplies (4/4) Covance CLS Investigator Manual
Provided in English
Protocol-specific:
Laboratory Visit Test Schedule
Mock laboratory requisitions
Specimen collection and processing information
Packaging and shipping instructions
Laboratory certifications
Renewals to be found at
Holiday Observances
Covance CLS contact information
Courier contact information
Section to file Covance CLS communications
Review manual prior
to first subject visit

11. Collection Kit Use and Inventory Management

12. Review for expired kits in preparation of visits
Kit Inventory Review
Kits are automatically resupplied, except:
Lost, damaged or expired kits
Check inventory carefully and request replacement kits
Allow enough delivery time before scheduling subjects
Inform Covance CLS of lost, damaged or expired kits to ensure automatic resupply functions properly
Review for expired kits in preparation of visits
Expiration
Date

13. Automatic Kit Resupply
Contact Covance CLS
to adjust / stop
automatic resupply

14. Covance CLS Resupply Requests
Request the following supplies from Covance CLS:
Replacement of damaged, lost or expired kits
Shipping supplies
Secure website
Confirmatory  sent providing
the work order reference number
Allow a minimum of 7 working days for the delivery
of your resupply order
Order supplies online:

15. Interchanging kits or kit components can lead to test cancellations
Accession Number
A unique identifier assigned
to each kit (example: R593812)
Protocol, site number and visit
name are encoded
Located on:
Kit box
Requisition
Each tube and vial
1 Accession Number per kit
Reference this number with queries to Covance CLS
Do not interchange kits between sites or protocols
Do not interchange tubes between kits
Interchanging kits or kit components
can lead to test cancellations

16. Collection Kit Content (1/2)
Contents are specific to visit on kit label
Requisitions
Collection tubes and transport vials
Pre-labeled with test names
Needles and holders
Packaging materials
Incorrect or missing subject identifier could cause cancellation of testing
To label replacement tubes and vials
Discard if not needed
Write the test name and subject identifier on label
SM8 Serum CAP
1234
Write subject’s identifier on labels
when drawing specimens
2 extra bar coded labels
SM8 Serum CAP
1234

17. Collection Kit Content (2/2)
CTC/CAP and Day 1 Kits
Include one of each of the following for CTC samples:
10 mL CellSave Preservative Tube
Green bar printed on label
21-gauge butterfly needle
Specimen Collection Bag
Samples collected with these kits are shipped to Covance CLS and Genentech
Specimen details provided on slides of this presentation

18. Requisition Completion

19. Laboratory Requisition (1/2)
Completion is mandatory for sample
processing
Provided in English
Use a black ballpoint pen
Draw single line through incorrect information
Date and initial correction
Includes:
Subject demographic section, special instruction(s), administrative question(s)
Optional testing: check box to order testing
Collection instructions and shipping condition when not enough space on 1st page

20. Laboratory Requisition (2/2)
NCR Copies
3-Part NCR (CTC/CAP and Unscheduled):
Ship white copies to Covance CLS
Ship pink copies to Genentech with CTC/CAP
Retain yellow copies for your records
2-Part NCR (all other visits):
Retain pink copies for your records

21. Laboratory Requisition Completion (1/2)
Completion of demographics is mandatory for sample processing
Clear + Consistent + Complete = Query Free Requisitions
To identify subject
G E N E R I C
To calculate specimen stability
To assist in site communication

22. Laboratory Requisition Completion (2/2)
Provide information using check boxes
or written entries
CTC/CAP and Arm C/D Urine DNA requisitions
Is patient on or off study treatment?
C1D1, C1D8, C6D1/C3XD1 and Unscheduled requisitions
Provide PK collection date and time
DD/MMM/YYYY and 24 hour clock
Optional Testing
Mark appropriate check box to identify testing to be performed
Incomplete information triggers queries

23. Use of Unscheduled Kits
C6D1/C3XD1
This kit is used to draw the GDC-0941 PK samples for patients at C6D1 or crossover patients at crossover Cycle 3
Arm C/D Urine DNA
This kit is used to draw the Urine Tumor DNA for Arm C and D patients for all visits after Screen where the Urine Tumor DNA is collected
This includes regular visits and crossover visits
CTC/CAP
This kit is used to draw the CTC and plasma and serum CAP samples every six weeks starting at C1D1
Unscheduled
This kit is used to draw unscheduled samples that have been approved by the CRO

24. C1D1 Visit
Pharmacogenetic, CTC/CAP and Urine DNA samples must be drawn pre-dose
In addition to collecting C1D1 kit, also collect
CTC/CAP kit for all patients
Urine DNA kit for all Arm C/D patients
The Pharmacogenetic sample is required for all patients unless the local regulatory agency prohibits drawing the Pharmacogenetic sample

25. Specimen Collection and Packaging

26. Specimen Types Returned to Covance CLS
Frozen
Serum √
Plasma
Whole Blood
Urine
Visit test schedule (table of tests per visit) provided in:
Study Protocol
Covance CLS Investigator Manual
Detailed collection and handling instructions provided in:
On requisitions within kits

27. Specimen Management (SM)
Testing not performed and not reported by Covance CLS
Upon sample receipt Covance CLS will:
Register samples in Covance CLS tracking system
Verify subject’s ID and sample condition
Store samples at appropriate temperature
Forward samples to specified laboratory for analysis on schedule directed by Genentech

28. Collection Key Points (1/3)
Good Quality Data Begins With Good Quality Samples
Select proper collection tube(s)
Thoroughly mix blood by inverting tube
Do not draw whole blood samples first
Avoids potential tissue thromboplastin contamination and clotting
Serum
Allow blood to clot upright for 30 minutes
Urine
Provide adequate sample volume; cap tightly

29. Collection Key Points (2/3)
Centrifugation
Room temperature: Serum CAP
+2 to 8°C: Plasma samples
Tubes may be centrifuged under ambient condition (room temperature) if a refrigerated centrifuge is not available
Proper speed and time
Refer to Covance CLS Investigator Manual for specific settings
May vary from sample to sample
Example: minimum of 1500 x g for 15 minutes
Clot and serum must be well separated
Cells and plasma must be well separated
Do not centrifuge when testing requires whole blood or urine samples
Use pipette provided in kit to transfer serum/plasma into proper pre-labeled aliquots
Plasma: Avoid the red cell layer
Specimen transfer

30. Collection Key Points (3/3)
Storage and shipping condition
Frozen -70°C
If -70°C not available, samples may be stored at -20°C for up to one week
Day of collection
Back up samples shipped within 1 week
Place the collection tube in an ice/water bath and maintain chilled until centrifugation
Centrifuge within 60 minutes of collection
Transfer plasma into PRIMARY and BACKUP vials
Shipping frequency
Special PK processing/ instructions

31. Samples Not Returned to Covance CLS (1/2)
Specimen Type
Ambient
Whole Blood
CTC
Avoid backflow from CellSave tube during collection
Place the patient’s arm in a downward position
Hold the tube with the stopper upmost
Make sure the solution inside the tube does not touch the stopper or end of the needle during venipuncture
Mix tube immediately to prevent clotting
Inadequate or delayed mixing may result in inaccurate test results 31

32. Samples Not Returned to Covance CLS (2/2)
Specimen Type
Ambient
Whole Blood
CTC
Return CTC samples ambient to Genentech with pink copy of the requisition
Use the shipping supplies provided by Covance CLS
Ship Monday through Wednesday to:
Genentech Sample Management 550 Grandview Drive BLDG 47, Room 1230 (471230) South San Francisco, CA 94080
Do not return samples to Covance CLS

33. CTC Packaging Key Points
CTC Shipments to Genentech
Follow details provided in Covance CLS Manual
Required materials provided within the shipping box or in Covance kit
BM01DA Shipping Box
BM08WFA Foam Liner
BM08AV Bubble Mailer
BM08GEL Gel Pack
The BM08GEL Gel Pack needs to
rest in ambient conditions for 72 hours
prior to pack-out
Pressure Bag (provided in Covance kit)
Absorbent (provided in Covance kit)

34. Packaging Key Points (1/4)
Insert tubes into Specimen Collection Bag
One Accession Number:
Per Specimen Collection Bag
Per shipping temperature
Include white copy of requisition in outside pouch (make bar code visible) with ambient samples

35. Packaging Key Points (2/4)
Ambient samples
Prepare Gel Pak (thermal insulator) to insulate ambient samples
Take Gel Pak from kit
Fill to indicated line with ambient water
Let gel form or massage absorbent pack until gel forms
Evenly distribute gel in bag while expelling air
Seal tightly
Wrap Gel Pak around Specimen Collection Bag containing ambient samples
Do not place specimens directly into gel

36. Packaging Key Points (3/4)
Frozen samples
Place Specimen Collection Bag in Styrofoam container
Group shipments as much as possible
Use recommended amount of dry ice
Completely surround samples with dry ice

37. Packaging Key Points (4/4)
If a combination box being used
Ambient + Frozen
Place ambient samples in dedicated section of shipping box
Replace lid and close box securely
Place site’s address label on shipping box
Pre-printed with site’s address and provided by Covance CLS
Attach shipping documents to outside of box
Keep a copy at the site
All shipping conditions

38. Sample Processing Delays
Reasons for processing delays
Missing, incomplete or inconsistent data on requisitions
Incorrect subject identifiers on returned containers
More than one subject per Accession Number
Incorrect visit kit used
Incorrect sample condition
Covance CLS will query the site
Samples will not be shipped to referral lab until all queries are resolved
Sample processing will be
performed upon receipt of the samples 38

39. Courier Arrangements

40. Courier Information
To Covance
To Genentech
Canada US
Ambient
N/A
Fed Ex
Frozen
UPS
Dry Ice Provider
Site
Courier contact information is communicated to the sites in Covance CLS Investigator Manual
US only: United Parcel Service (UPS)
Saturday morning pickups
Confirm Saturday availability/pickup time with UPS
Delivered to Covance CLS on Sunday
US and Canada: Locate dry ice supplies (site’s responsibility)
IATA certification may be required for dry ice shipments per country regulations
Consolidate shipments when possible
Time and cost effective

41. Shipping Documents (Canada)
Air waybills and Commercial Invoices
Commercial Invoice
Provided pre-printed by Covance CLS
Complete required information
Send/attach to appropriate shipping box
Ensure Commercial Invoice is included to avoid delivery delays
If shipping on Friday, check “Saturday Delivery” on air waybill

42. UPS Shipping Labels (US)
Provided pre-printed by Covance CLS
Dedicated to Covance CLS shipments
Use dedicated UPS phone number ( ) to schedule pickup
Attach to appropriate shipping box
Courier details in Covance CLS Investigator Manual
Ensures Friday shipments
to be delivered on Saturday

43. Pickup Information Prior to first shipment to Covance CLS, contact
your courier to determine/confirm:
Last Call Time, latest time to schedule same day pickup
Last Pickup Time, latest time for courier pickup
Transit Time to Covance CLS
Provide exact pickup location
Transit Time to Covance CLS:
24 hours sites: Ship Monday through Friday
48 hours sites: Ship Monday through Thursday
Consider customs/local holidays before shipping
Refer to Covance Central Laboratory Investigator Manual or
Do not ship one day before holidays (2 days if inbound transit is 48 hours)
If sample pickup is missed, FROZEN samples remain at instructed temperature
Contact Covance CLS Investigator Support Services
if you need further advice

44. Contacting Covance CLS

45. Who to Contact Contact Covance CLS Contact courier
To add/change information at investigator’s site
Contact telephone and fax numbers
Covance’s CLS supplies delivery address
Sample pickup address
Query resolution
Resupply
Place orders
Adjust automatic resupply
Stop automatic resupply when enrolment is complete
Courier issues
To order pickup
To track packages
Contact courier

46. Primary Reference Material
Refer to Covance CLS Manual
Covance CLS contact information
Toll Free and Direct Numbers telephone numbers
If Toll Free unavailable, call telephone operator for collect call to Covance CLS
Courier contact information
Sample collection instructions
Packaging instructions

47. THANK YOU !