Boehringer Ingelheim 1230.14 Covance Central Laboratory Procedures Toronto 23 February 2013...

Boehringer Ingelheim

1230.14Covance Central Laboratory Procedures

Toronto 23 February 2013

Investigator’s Meeting

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.

Confidential

Central Laboratory Topics

Pharmakokinetic samples

Collection Summary Overview

Pharmacogenomic samples

Cytogenetic samples

Supplies

3

Confidential

• Kits are visit specific

• 1 Kit at C1 V1: Pharmacokinetic & Pharmacogenomic• 1 Kit for Pharmacokinetic samples at

» C1 V3

» C2 V1o C4 V1, o C6 V1

• Envelope and labels for Cytogenetic samples (blood and BM)

• Bone marrow central review => From Quest to Quest

Summary Overview

4

Confidential

• When? – Before start of infusion of Volasertib/ Placebo– Just before the end of infusion of Volasertib/ Placebo

– Cycle 1 Day 1 & 15– Cycle 2 Day 1– Optional at Cycle 4 Day 1 & Cycle 6 Day 1

• Remind:– after ECG– from the arm opposite to the infusion arm (or either forearm in case of central venous

access)– record exact times (Objective is evaluate relation between PK‘s and ECG‘s Use the

same watch for the ECG and the PK (use the ECG clock time to document PK sampling time or make sure the watch used to document PK sampling time shows the same clock time as the ECG machine) to allow correlation of ECG and PK

PharmacoKinetic samples

5

Confidential

• Fill in all the required information on the appropriate labels of the two cryo tubes each for plasma. Please verify that the information given on the labels corresponds to the current visit, time point and patient n°.

• Prepare plasma by centrifugation at approximately 3000 rpm (2100 g) for 15 minutes at 4 – 25°C / 40 – 77°F (preferably at 4°C / 40°F). Centrifugation should be done within 60 min after sampling!

• Transfer immediately with a single use transfer pipette two plasma aliquots, one in each of the two labeled cryo tubes (at least 500 µL plasma in each tube). Make sure that the sample tubes are tightly closed.

PharmacoKinetic samples (SM 1)

Plasma Preparation

6

Confidential

• Store the aliquots in upright position in the appropriate cryo box (one box for aliquot 1 & one box for aliquot 2) immediately at -20°C / -4°F or below until shipment.

• If possible store the cryo boxes for aliquot 1 and aliquot 2 samples in different freezers.

• The temperature of the freezers should be monitored daily.

• Thawing of the samples should be avoided. When samples unexpectedly thaw due to the freezer being unable to maintain the necessary temperature, the samples should be re-frozen as soon as possible and the trial team must be informed about this occurrence (Conditions e.g. temperature of freezer when discovering the incident and duration e.g. last checked and OK on DATE and TIME; problem detected on DATE and TIME; duration of the issue).


Sample Storage

7

Confidential

• Wherever possible samples should be shipped on Monday, Tuesday or Wednesday to ensure prompt delivery during week days before Saturday. Make sure the samples will not arrive on weekends or public holidays.

• Never send aliquot 1 and aliquot 2 of the same sample within the same shipment.

• Shipment of the frozen PK samples to Covance should take place every 3 months together with PGx samples.

• For packaging see the “Packaging Procedures” in the “Central Laboratory Service Manual” provided by Covance & Order dry ice on time (see Covance manual)


Shipment of the frozen PK samples

8

Confidential


• Provided in English

– All information should be completed in English

• Complete all required information and answer questions

• Collection instructions and shipping condition

• Ship white copies to Covance CLS with frozen PK aliquot 1 samples and PGx samples

• Ship yellow copies to Covance CLS with frozen PK aliquot 2 samples

• Retain pink copies for your records

Completion of requisition forms

9

Confidential

Pharmacokinetic

Laminated card

10

Confidential

• When?– Ideally at Cycle 1 Day 1 (could also be taken at any later visit)

• Remind:

– Patient must have signed a separate ICF

– Optional participation

Pharmacogenomic sample

Tubes are part of PK Kit (C1V1)

11

Confidential

• Prepare the provided blood drawing tubes• 2 mL EDTA whole blood tube (SM 2 PGxA)• 8.5 mL PAXgene DNA tube (SM 3 – PGxB)

• Fill in all the required information (patient number; date of blood collection) on the appropriate, pre-printed label on the blood drawing tubes. Please verify that the information given on the label corresponds to the current patient, visit and date.

• Draw the blood samples into the provided blood drawing tubes.

• Invert gently about 10 times, avoid vigorous shaking.

• Carefully complete all required information on the “Laboratory Requisition Form for PGx” (provided by Covance).

Pharmacogenomics samples (SM 2 & SM 3)

Blood Sampling

12

Confidential

• Freeze the PGx blood samples immediately at -20°C / -4°F in upright position in the appropriate cryo box.

• Store the cryo boxes at -20°C / -4°F or below until shipment.

• The temperature of the freezers should be monitored daily.

• Thawing of the samples should be avoided. When samples unexpectedly thaw due to the freezer being unable to maintain the necessary temperature, the samples should be re-frozen as soon as possible and the trial team must be informed about this occurrence (Conditions e.g. temperature of freezer when discovering the incident and duration e.g. last checked and OK on DATE and TIME; problem detected on DATE and TIME; duration of the issue).


Blood Sample Storage

13

Confidential

• Wherever possible samples should be shipped on Monday, Tuesday or Wednesday to ensure prompt delivery during week days before Saturday. Make sure the samples will not arrive on weekends or public holidays.

• Shipment of the frozen PGx blood samples should take place always together with the frozen PK samples.(3-monthly).

• For packaging see the “Packaging Procedures” in the “Central Laboratory Service Manual” provided by Covance.

• When shipping the samples on dry ice to Covance, please include the completed and signed “Laboratory Requisition Form for PGx”.

• Send the samples together with the appropriate documents (Requisition Form, List of contents) to Covance : See lab addresses reported in the shipping instruction provided with the investigator manual.


Shipment of the frozen PGx Blood samples

Similar procedure as for PK

14

Confidential

Pharmacogenetic sampling

Laminated card

15

Confidential

• When?

– Diagnosis (screening)

– At every BM assessment:

• From Cycle 2 Visit 5, and every other cycle (C4V5, C6V5, C8V5, etc)

• In case of suspicion of relapse or progression

• EOT

• Remind:

– Must be shipped on the day of collection, directly to Ulm university

Cytogenetic samples

16

Confidential

• At SCREENING , before the study treatment starts, collect for Cytogenetic and Molecular genetic diagnostics:

– 40mL of peripheral blood, – 5-10mL bone marrow (10 mL if ever possible), – and 10mL of blood (EDTA) for plasma preparation

• For this procedure usual, sterile 10mL syringes (please use your clinic material) can be used.

• Before filling the tubes it is necessary to have Heparin already in the syringes for anticoagulation.

– for bone marrow: 1:10 [500 IE Heparin-Na/mL sample] fill 1 sterile 10mL syringe with bone marrow

– for Heparin-Na-blood: 1:10 [500 IE-Na/mL sample] fill 4 sterile 10mL syringes with peripheral blood. Alternatively, standard syringes can

be used. If no Na-Heparin syringes are available, also Li-Heparin syringes can be used– for plasma preparation

fill a standard 10mL blood EDTA syringe (please use your clinic material)

Cytogenetic samples

Instructions for sampling

17

Confidential

After drawing of the samples:

• Please close all syringes with a disposable sealing cap.

• All syringes need always to be labelled with the special labels provided by Covance. Please complete the patient number and the date of sampling. Do not forget to mark the matrix of the sample.

• Labelling of the samples:

Matrix: = Bone marrow, Blood, Plasma (mark it)Last name: = BI 1230-14 (preprinted)First name: = _ :_ _ _ _ (patient number) Date of birth: = 01.01.2000 (dummy date of birth for all patients – preprinted)Date of sampling |__||__|/|__||__|/|__||__|

day month year

Cytogenetic samples


18

Confidential

• Complete the “Material delivery Form” available in the Covance Lab Manual:

Original copy shipped with samples

Store a copy at site, in ISF

Cytogenetic samples


19

Confidential

Cytogenetic samples


20

• Before shipping to Ulm:

ensure your site is faxing the requisition form to Ulm (or e-mail)

So that shipment is expected and handled immediately on receipt

Confidential

• All syringes have to be packed according to the Lab manual from Covance,

• and sent to the laboratory Prof. Dr. Döhner (University Hospital of Ulm- Germany)

• If possible the samples have to be at the reference laboratory within 24 hours (up to 48 hours)

• Shipped the day of collection

Cytogenetic samples


21

Confidential

• Results will be sent back to sites

• Results are uploaded in eCRF by Ulm Laboratory

=> no need for site staff to enter Cytogenetics’ results in eCRF

Cytogenetic samples

Results

22

Confidential23

Important

If a patient actively withdraw the Informed Consent for biobanking of cytogenetic samples,

please fill in the separate document “Withdrawal of the Informed Consent

Fax it to Ulm

File in ISF the returned signed faxed from Ulm

Cytogenetic samples

Withdrawal of consent

Confidential

Cytogenetic and Molecular Genetic Diagnosis

Laminated card

24

Confidential

• Type of labkits provided at initial supply (3 of each)– PK

• Cycle 1 Day 1 (with PGX tubes), • Cycle 1 Day 15, • Cycle 2 Day 1, • Cycle 4 Day 1 • Cycle 6 Day 1

• Bulk supplies– 1x Lab Manual and Quick Reference Guide– 4x Miscellaneous labels for cardboard racks– 2 x Cardboard racks (81 spaces) for PK samples– 2 x Cardboard racks (25 spaces) for PGx samples– 5x Envelopes and miscellaneous labels for Cytogenetic samples shipped to Ulm/Germany

Review packing list within initial shipment

25

Initial Supplies

Confidential

Initial Supplies

• Shipping boxes

• Site specific shipping documents – Airway bills, Commercial Invoices, return address labels

• Shipping supplies are provided by courier or Covance CLS, depending on courier arrangements

– Refer to Covance CLS Investigator Manual and courier arrangements fax for country specific information

Shipping supplies

26

Confidential

Covance CLS Resupply Requests

• Replacement of damaged, lost or expired kits• Shipping supplies (except when delivered by the courier)• Extra bulk supplies

• 18 working days in Russia• 20-22 working days in Latin America

• Secure website• Confirmatory e-mail sent providing

the work order reference number

Request the following supplies from Covance CLS

Allow a minimum of 7-9 working days for the deliveryof your resupply order, except:

Order supplies online:www.covance.com/kitordering

27

Confidential

Please review the Covance CLSInvestigator Manual prior to first patient visit

Primary Reference Material

• Covance CLS contact information– Toll Free and Direct telephone numbers

– If Toll Free unavailable, call telephone operator for collect call to Covance CLS

• Sample collection instructions• Packaging instructions

28

Confidential

Key Points to Success / Lessons Learned (1/2)

• Initial Supplies – Complete and submit requested information forms

– Check packing list

• Resupply Process– No automatic resupply– Check your inventory periodically

– Please allow the minimum of 7-9 working days for delivery of resupply orders

• Collection kits– Select appropriate kit, always check expiration date

– Properly label all tubes/vials sent to Covance CLS

• Requisitions– Submit Clear-Consistent-Complete & Query Free

Requisitions

29

Confidential

Key Points to Success / Lessons Learned (2/2)

• Sample Processing– Follow instructions on requisitions and in manual

• Packaging– Use Covance CLS/courier provided boxes

– Order the dry ice early enough for your frozen shipments (some sites require 2 working days advance notice)

• Shipping– Contact courier for pickup in advance

• Contact Covance CLS for:– Laboratory questions

– Courier issues

30

Boehringer Ingelheim 1230.14 Covance Central Laboratory Procedures Toronto 23 February 2013...

Documents

Transcript of Boehringer Ingelheim 1230.14 Covance Central Laboratory Procedures Toronto 23 February 2013...