1. business and industrial
2. business operations
3. business plans

PROPOSED LAB MANUAL TEMPLATE
Introduction
This document has been prepared as a guide to help in the preparation of
laboratory manuals used by Phase I Units / Central Laboratories to assist in
labelling, sample collection, handling, storage, shipment and retention of
biological samples generated in Phase I or Multi-Centre PK Clinical Trials.
There is no regulatory requirement to follow the suggested process.
Companies should feel free to adapt the generic template to their own
requirements and the extent of the detail should reflect the specific needs of
individual projects and studies. The document has been generated because it
is felt within the EBF community that a ‘generic’ approach to the drafting of the
Lab Manual will help to raise standards across the industry.
Red text highlighted in yellow is added as prompt information only and should
not be included in the final study manual.
PK Lab Manual for Clinical Study XXXyyy-123 CONFIDENTIAL
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TITLE PAGE
Study No: xxxx
Sponsor Name: XXXXXXXXXXXXXXXXXXXX
Clinical Study Protocol Title:
Example : An open-label Phase I dose-escalation study to evaluate the safety, tolerability, maximum
tolerated dose, pharmacokinetics, and pharmacodynamics of the xxx in subjects with xxxx
Date: DD-MM-YYYY
Clinical Study Phase: xx
Protocol version: xx
Protocol date: DD/MM/YYYY
Study Manager: XXX
Author: XXX
This document should serve as a source of information regarding, labelling
collection, handling, storage, shipment and retention of biological samples
(Pharmacokinetic/PK) in clinical trials.
It does not contain information regarding safety, clinical chemistry or
biomarker samples.
It should assist :
a. Pharmaceutical companies in gathering all required information
regarding PK samples
b. Central Laboratories and CROs in receiving all information regarding PK
samples
The further use of the document may be as a source of information for
database set up, creation of CRO formatted handling instructions or as a
manual for CRO. This is at the discretion of the Central Lab / CRO
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TABLE OF CONTENTS
TABLE OF CONTENTS .............................................................................................. 3
1. DOCUMENT HISTORY ........................................................................................... 4
2. PURPOSE AND SCOPE ......................................................................................... 4
3. CONTACTS / KEY PERSONNEL/ RESPONSIBLE STAFF .................................... 4
4. DOCUMENTS / INFORMATION ............................................................................. 5
5. SUPPLIES ............................................................................................................... 6
6. EQUIPMENT ........................................................................................................... 7
7. LABELLING ............................................................................................................. 8
8. SAMPLE HANDLING AND COLLECTION PROCEDURES .................................... 9
8.1 Blood/Plasma/Serum Samples (complete a separate subheader for each matrix
type) ............................................................................................................................ 9
8.2 Urine/ Faeces Sample Collection and Processing ............................................... 10
9. STORAGE AND STABILITY ................................................................................. 11
10. SHIPPING ........................................................................................................... 12
11. SAMPLE DISPOSAL ........................................................................................... 13
12. SIGNATURES ..................................................................................................... 13
13. APPENDIX .......................................................................................................... 14
Appendix 13.1. Example of a Sample Shipment List/Sample Inventory (delete
unnecessary columns as appropriate) ....................................................................... 15
Appendix 13.2. Example Sample Receipt Form ........................................................ 16
Appendix 13.3. Urine Handling Sheet Example (amend as appropriate) .................. 17
Appendix 13.4. Centrifuge Adjustment Conversion Table – Relationship between rpm
and RCF .................................................................................................................... 18
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1. DOCUMENT HISTORY
Version
version 1
version 2
Date
23.01.2014
19.02.2014
Description of change
protocol version 1.0
amendment 2
2. PURPOSE AND SCOPE
This lab manual applies to clinical study number: xxxxxxx, title:…….
This lab manual describes the processes for the labelling, collection, processing, storage and
shipment of blood/plasma/serum/urine/ (biological) samples for PK analysis.
The specifications can be used as basis for a lab manual (Phase I units) and
statement of work (central laboratories) (Remove this text prior to finalisation).
3. CONTACTS / KEY PERSONNEL/ RESPONSIBLE STAFF
Definition of Key Contacts
 Sponsor Clinical Study Manager: Responsible for trial management at the sponsor.
 Early Phase Clinical Unit Study Manager / Project leader: Responsible for the trial
management in the clinical unit.
 Sponsor Sample Management: Responsible for sample logistics for samples shipped to the
sponsor.
 Sponsor Bioanalytical Lead: Accountable for the quality and delivery of the PK bioanalytical
data.
 CRO Bioanalytical Lead: Responsible for the quality and delivery of the PK bioanalytical
data if sourced to an external provider.
Sponsor Clinical Study Manager
Name and Address
Title
Email
Phone/Fax number
Early Phase Clinical Unit Study Manager / Project Leader
Name and Address
Title
Email
Phone/Fax number
Sponsor Sample Management
Name and Address
Title
Email
Phone/Fax number
Sponsor Bioanalytical Lead
Name and Address
Title
Email
Phone/Fax number
CRO Bioanalytical Lead
Name and Address
Title
Email
Phone/Fax number
Other Laboratory Contact (As required, e.g. CRO for Lab Diagnostics)
Name and Address
Title
Email
Phone/Fax number
PK Lab Manual for Clinical Study XXXyyy-123 CONFIDENTIAL
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Page 5 of 18
It is important that all people listed here have input into this document. (Remove prior
to finalisation)
4. DOCUMENTS / INFORMATION
Documents that should be supplied prior to sample collection if applicable:
Document
Available at Clinical Unit Available at Bioanalytical Lab
Clinical Protocol
Subject List
Data Reporting Template
Data Management Plan
Randomisation List (if
applicable)
Randomisation Code
(Shared by Sponsor Stats
group with bioanalytical lab)
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Document for sample storage (if applicable to the Site)

Sample Storage document
The following information will be included on the Sample Storage Document







Study (short) title
Study number
Matrix type (plasma/serum/whole blood/urine/other)
Sample type(primary/back-up/PK)
Sampling date (DD-MMM-YYYY format) and scheme time
Date in/Date out
A new form will be used per study (sub) group
Documents that require completion prior to sample shipment:

Sample Shipment List / Sample Inventory (see Appendix 13.1)
Additional information to be sent with the shipment as a minimum [amend as appropriate]:
 Fill number of samples, per matrix type.
 Record the AirWay Bill Number.
 Date and Sign the form.
 E-mail a copy to Bioanalytical Lab or Central Lab (if required).
The Sample Shipment List/Sample Inventory (see Appendix 13.1) should be added to the
shipment and should be QC checked against the sample tube labels within the shipment,
prior to transportation between any clinical or laboratory facilities as well as on arrival.
At least on the day of shipment of the samples the following documents must be available, if
applicable:

Detailed (electronic) Sample shipment list in e.g. Excel format; this list should contain
all sample identifiers that are required for reporting of the results.

Detailed (electronic) shipment list in appropriate LIMS design (upload file) or for
export from LIMS.
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5. SUPPLIES
A. Sample Collection Tubes:
Sample /
Matrix Collection
Analyte
Tube/
Container
PK Analyte X
PK Analyte Y
Blood
Blood
PK Urine
Analyte X
Tissue
24 hr.
Urine
Tissue
K2EDTA
B. Aliquot / Transport Tubes:
Sample Matrix Containerb
PK
Plasma
Analyte X
PK
Plasma
Analyte X
PK
Plasma
Analyte Y
PK
Plasma
Analyte Y
PK Urine Urine
Analyte
X+Y
Cryotube
Volume
Supplier
Part #
Reference #a
Comments
2 mL
4 mL
Volume Supplier
(#)
1.8 mL
(x1)
1.8 mL
(x1)
2 mL
(x2)
2 mL
(x1)
20 mL
(2x)
Part # /
Capb
a
Reference #
Comments
Primary
Backup
Primary
Backup
Indicate ‘or equivalent’ if acceptable as ‘Part Number/ Reference number’ may be specific to a global
region.
b Indicate additional specifications below, if applicable
a
C. Additional Supplies and/or Specifications:

Sample Collection Specifications
 Examples:
Needles, if specific requirements are applicable
PK analyte cryotube: round bottom, self-standing, star-footed, internal thread
Cap: colored
Disposable transfer pipette: Indicate the type of material required if applicable

Site Storage Container Specifications:
 Examples:
Box with gridded insert to hold cryotubes upright
Tissue block holder
Box for maintaining separation between samples and freezer walls in
automatically defrosting freezers
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6. EQUIPMENT
A. Investigator Site Equipment

Centrifuge:
Temperature: Room Temp, 4°C-8°C
Speed: (1500 to 2000 x g), (1500 to 4000 x g)

Freezer:
Controlled temperature: approximately -20°C or below freezer.
Non-automatically defrosting (Indicate alternative supplies in section 5 for maintaining
constant temp, if applicable).
Controlled temperature: approximately -70°C or below.

Controlled Refrigerator (for chilling collection tubes, if applicable).

Electronic Ice Bucket (or chipped ice alternative for processing, if applicable).

Dry Ice (for handling frozen samples, if applicable).

Indicate if/if not ok for samples to be stored in dry ice on day of collection.
B. Attachments Related to this Section:

RPM / RCF graph (see Appendix 13.1).
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7. LABELLING
Biological samples such as blood/plasma/serum/urine/CSF/biopsy,saliva samples for PK
evaluation must be labelled with pre-printed, freezer-safe labels containing the following
information [Amend as appropriate]:
Please complete one table per analyte:
Possible
Information
Sponsor Study
Number
Mandatory?
Please tick:
Yes
No
Pre-Printed?
Please tick:
Yes
No
Subject Number
Yes
No
Yes
No
Period/Cycle
Yes
No
Yes
No
Treatment
Yes
No
Yes
No
Visit
Yes
No
Yes
No
Nominal Day and
Time
Yes
No
Yes
No
Analyte
Yes
No
Yes
No
Matrix
Yes
No
Yes
No
Aliquot (Name)
Yes
No
Yes
No
Barcode
Yes
No
Yes
No
If necessary, please
specify:
Label all tubes in the same manner.
Barcodes should be placed vertically.
Example of a pre-printed PK plasma label and its placement:
Study
Site
Subject
Day 1 Predose
Analyte
Plasma
Aliquot
Please confirm if a specific marker is required for completion of the label!
Please confirm if additional clear tape (e.g. liquid nitrogen resistant) is required or prohibited!
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8. SAMPLE HANDLING AND COLLECTION PROCEDURES
All text in blue requires update, standard options have been added where applicable for ease of
completion.
A separate sub-section should be completed for each type of sample. The text below may be moved
into relevant sections but if applicable to all sections should remain in this area to avoid
duplication.
8.1 Blood/Plasma/Serum Samples (complete a separate subheader
for each matrix type)
Blood samples for determination of [analyte name] will be collected at the timepoints detailed
in [Section xxx] of the clinical protocol and processed as follows:
Blood/Plasma/Serum SAMPLE COLLECTION
Any specific conditions
Blood sample tubes to be chilled before use
Blood samples to be protected from light
Blood samples should be inverted X times to ensure mixing
Blood samples to be collected on ice
Any stabilisers to be added?
Volume blood draw
required
x mL
Sample collection tube
anticoagulant of tube, include details of tube size
Plasma tube
Include details of the tube size and type (e.g. polypropylene)
SAMPLE PROCESSING
Sample processing

Sample to be processed/centrifuged/ refrigerated/frozen at
X°C within x min of the time of collection
For serum / plasma samples include the below as required. For
whole blood samples delete the below

Leave samples to stand for 30 minutes at X°C/ ambient
temperature prior to centrifugation. (serum only)

Centrifuge at x g for x min at X°C (or ambient temp)
Include any details of stabilisers to be added to plasma tubes

Transfer samples equally into x tubes (insert number)

Ensure that the primary tube contains x mL plasma / serum

Sample to be stored at X°C within X minutes of collection
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Page 10 of 18
8.2 Urine/ Faeces Sample Collection and Processing
Urine samples for the analysis of [analyte name] will be collected at the time points detailed
in [Section xxx] of the clinical protocol.
Detail any specific sample collection procedures here (see Appendix 13.1, Urine Handling
Sheet)
URINE/FAECES SAMPLE COLLECTION
Any specific conditions

protected from light

addition of surfactants / stabilisers : [addition of surfactants /
stabilisers as required e.g. 1% Tween 80 Aqueous Solution
(v/v) to be added to bulk prior to aliquots being removed, to
give 0.1% Tween v/v (see urine handling sheets in Appendix
13.3), Ensure sample is well mixed.].
Duplicate sample required
Yes / No (remove this if pooling taking place at a different lab)
Volume required
X mL (primary) X mL (back-up) (remove this if pooling taking
place at a different lab)
Sample collection
container
Urine will be collected into individual [polypropylene – type to be
specified and any additives required] containers and stored at
40C during the collection interval.
Include details of sample storage conditions prior to shipment
here if the below section is not required.
Aliquot tube
X mL polypropylene/ polyethelyne tubes
SAMPLE PROCESSING (delete this section if bulk samples / individual voids are
shipped to an analytical lab)
Sample processing

Before transferring, if combining urine/faeces collections
ensure appropriate mixing has taken place and the total
volume or weight (using SG=1) has been recorded.

Transfer urine/ faeces into X appropriately labelled
polypropylene tubes. The primary and duplicate samples
should contain XmL of urine.

Fill tubes ensuring that sufficient gap remains e.g. no more
than ¾ full at the top of the samples for required sample
mixing.

Sample to be stored at X°C during multiple collections, then
pooled, mixed, aliquoted and frozen at X°C.
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9. STORAGE AND STABILITY
Refrigerators/freezers must be temperature controlled. Please ensure that primary samples
and backup samples are stored in different refrigerators/freezers.
Store blood/plasma/serum/urine at room temperature/refrigerated/frozen at –20°C or lower /
–70°C or below. [please select]
Storage and stability information on test item is as follows:
Analyte
Matrix
Plasma
Storage
temperature
below -20°C
Stability data
(optional)
24 months
Compound A
Compound B
Serum
below -70°C
36 months
Compound C
Urine
below -20°C
24 months
and/or:
* Blood/plasma/serum/urine stability investigations ( - XX°C for at least XX days) are still
ongoing (delete as appropriate).
The primary blood/plasma/serum/urine samples are to be stored at the site/central lab until
shipment [please select]. (Please refer to section 10 for shipment frequency).
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10. SHIPPING
A separate sub-section should be completed for each type of sample (e.g. PK). The text
below may be moved into relevant sections but if applicable to all sections should remain in
this area to avoid duplication.
Follow all required shipping regulations (confirm with courier what is required). Frequency of
shipping will be every X months (amend as necessary).
Information
Shipment date
Mandatory?
Please tick:
Yes
No
Done?
Please tick:
Yes
No
Notification to recipient
Yes
No
Yes
No
Tracking number provided
Yes
No
Yes
No
Shipment scheduled to
arrive on working day
Manifest (Sample
Shipment List / Sample
Inventory) enclosed (as /
Appendix 13.1)
Shipment receipt form
enclosed (as / Appendix
13.2)
Package labelled with
study number
Frozen/refrigirated/ambient
shipment
Sufficient dry ice/cold
packs included
Temperature logger
required
Samples required to be
organized per subject
Shipment of back-up
samples
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
If necessary,
please specify:
When:
Expected delivery date
All pharmacokinetic/ Biomarker/ Total radioactivity plasma/serum/urine/ whole blood / faeces
samples (include type of analysis and matrix of matrices to be shipped) along with the
corresponding documentation, sample manifest and sample receipt form (for completion by
receiver) are to be shipped to:
Attn: Asterix the Gaul
Central Lab
Telephone: +33-(0)1234-456789
E-mail: [email protected]
This information should also be e-mailed to the above person at the receiving laboratory, as
also described in section 4.
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11. SAMPLE DISPOSAL
Blood/plasma/serum/urine samples will be stored at room temperature -20°C or below / 70°C or below in freezers with temperature monitoring prior to and after analysis until their
disposal is authorised by XXXX. The laboratory will retain documentation that includes
authorization and confirmation of destruction.
All samples will be destroyed X months after finalization of the bioanalytical report (only after
approval of XXXX).
For samples that have been taken without consent or are in excess the site should inform
XXXX. XXXX will confirm if the sample can be destroyed.
To request destruction of samples the site /central lab should complete a sample destruction
form and send it to XXXX.
12. SIGNATURES
We have reviewed this Lab Manual and agree with the content.
__________________________
A. Body
Sponsor Clinical Study Manager
_____________
Date
____________________________
A. Pipetman
Early Clinical Phase Unit Lead
_____________
Date
__________________________
A. Sample
Sponsor Bioanalytical Lead
_____________
Date
_________________________
A. Quality
CRO Bioanalytical Lead
_____________
Date
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13. APPENDIX
DD-MMM-YYYY
Page 14 of 18
PK Lab Manual for Clinical Study XXXyyy-123
Company Ref:
CONFIDENTIAL
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Page 15 of 18
Appendix 13.1. Example of a Sample Shipment List/Sample Inventory (delete unnecessary columns as appropriate)
Responsible Person:
Sponsor Clinical Study number:
Total number of samples:
Site
#
Box Barcode Study #
Pos
1
1234567 1234
Sub #
Period Treatment
101
1
20mg/kg
2
1235678
1234
101
1
20mg/kg
3
1246789
1234
101
1
20mg/kg
Remarks
Visit Collection Collection Time-point
Date
Time
and Split
1
DD-MMM- 08:45 AM
PK Pre-dose
YYYY
Plasma 1
1
DD-MMM- 08:45 AM
PK 1 hr
YYYY
Plasma 1
1
DD-MMM- 08:45 AM
PK 3 hr
YYYY
Plasma 1
Analyte
Specimen Type Specimen
condition
Analyte 1 Plasma
Frozen
Anticoagulant
Analyte 1 Plasma
Frozen
Anticoagulant
Analyte 1 Plasma
Frozen
Anticoagulant
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Appendix 13.2. Example Sample Receipt Form
Sponsor clinical study number
Pharma 1
Received from
US clinical site, brief address
Date shipped
DD-MMM-YYYY
Date and time received
Courier
Courier consignment number
Species and matrix
Human/plasma and urine
Total number of samples
120 plasma
40 urine
Dry ice remaining?
Samples frozen?
Sample manifest correct?
Sample discrepancies?
Condition of samples on
arrival
Serial Number Temperature
Data Logger
Samples received by
Signature
Date
DD-MMM-YYYY
Page 16 of 18
PK Lab Manual for Clinical Study XXXyyy-123
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Appendix 13.3. Urine Handling Sheet Example (amend as appropriate)
Subject No:__________ Initials: _________ Dose Date: ______________________________ Screening No: _________
At end of collection period, record weight of specimen. Calculate the volume of 1% Tween 80 solution to be added to the specimen. Record the volume of surfactant solution
added to the specimen. Cap specimen bottle and shake well. Transfer 2 x 2mL aliquots and 1 x 10mL aliquot to pre-labelled polypropylene tubes. Freeze sample aliquots at 20°C.
If volume in collection period exceeds 1 pooled container, complete this action with each container starting a new sheet for the remainder (2 nd container) of the collection. Mix
roughly and combine the collection prior to taking the aliquots.
Timepoint
Weight of
container to
the nearest
decimal point
(g)
A
Total Weight of
container and
sample to the
nearest
decimal point
(g)
B
Predose
0 to 4 hours
4 to 8 hours
8 to 24 hours
Comments (Please quote timepoint):
Total weight
minus Weight of
container (B-A) =
net sample
weight to the
nearest decimal
point (g)
Calculate
volume (mL) of
1%Tween 80
to be added =
net sample
weight (g) / 10
Volume (mL)
of 1%
Tween 80
solution
added to
specimen
Confirm
sample
well
shaken
(yes/no)
2 x 2 mL aliquot
1 x 10 mL
aliquot
transferred to 2 x 3.5
mL tubes and 1 x
20mL tube (tick for
each)
Discard
the
remaining
(yes/no)
Initials
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Appendix 13.4. Centrifuge Adjustment Conversion Table – Relationship
between rpm and RCF