BIOBANKING

AND

BLOOD STUDY

FUNCTIONAL REQUIREMENTS DOCUMENT

Rakesh Kukatla and Shelley Tworoger

HARVARD SCHOOL OF PUBLIC HEALTH
BRIGHAM AND WOMEN'S HOSPITAL
BOSTON, MA
2007.

Rakesh Kukatla & Shelley Tworoger B3S Functional Requirements Document Page 1
 INDEX

1. Summary……………………………………………………………………… 03

2. Functional Requirements……………………………………………………... 04

BioBanking Functional Requirements………………………………... 04

Blood Study Functional Requirements……………………………….. 06

3. Life cycle of Blood Study project…………………………………………….. 11

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 Summary
Four large cohorts (of human participants, approx. 400,000) have been recruited and

followed at the Harvard School of Public Health, Brigham and Women's Hospital, and Harvard

Medical School since the mid 1970's. Over the course of this time period, biospecimens have

been collected from over 150,000 participants. Primary specimen types include blood (plasma,

white blood cell, red blood cell), tissue, toenail, urine, and cheek cell DNA. Each of the four

cohorts has its own set of storage and tracking systems. The present effort aims to integrate

these separate systems into a single unified biopecimen storage and tracking system. The

primary goals of this project are:

1. Improve storage and tracking of existing specimens and new aliquots made from existing

specimens.

2. Increase the ability of blood study personnel to efficiently access and process the samples for

sending to the analysis laboratory.

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 Functional Requirements
The functional Requirements can be thought of consisting of two layers: a BioBanking

layer and a Blood Study layer.

BioBanking:

BioBanking layer stores and tracks biospecimens for cohort participants. A number of

specimen types are available for the participants in the cohort. Important goals are to provide

easy access to samples and to maintain data integrity. The data and processes of this layer are

pretty standard and can be found in most LIMS systems. The system would need to provide

flexibility to incorporate existing BioBanking data from legacy systems (primarily in flat files or

Oracle) as well as new BioBanking data from future cohort participants. The specimens are

tracked for each individual cohort. Following is a more detailed listing of the functional

requirements of the BioBanking layer.

BioBanking Functional Requirements:

1. Storage of items and storage units.

Items are cryo vials (4.5ml, 1.8ml, 1.5ml, 1.2ml, 1.0ml, 0.5ml ), plates (96 and 384

wells) and Nalgene cups. Storage units are boxes, racks, freezers, shelves and cabinets.

2. Transactional tracking of items and storage units.

Transactional tracking of items and storage units include complete history-lineage

and derivatives, all checkins and checkouts.

3. Functional tracking of items and storage unit usage.

Functional tracking of items and storage units include quantity and percent empty or

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full.

4. Integrity checking of items and storage units.

Integrity checking would avoid all location conflicts with other items or storage units.

No two items or storage units can occupy the same location.

5. Individual and Batch insertion/deletion of items and storage units.

Creation and deletion of items and storage units by entering data into a single screen one

at a time or many at a time, by importing data from files, by copying and pasting data into

screens.

6. Individual and Batch moving of items and storage units.

Moving of items and storage units from one location to another by dragging and

dropping, by text entry of source and destination locations one at a time or many at a time.

7. Individual and Batch suspension/reservation of items and storage units usage.

Suspension or reservation of items and storage units by checking or unchecking one or

many at a time. When this happens these items and storage units are no longer available for use.

8. Individual and Batch editing of items and storage units.

Editing of items and storage units by selecting one at a time or many at a time.

9. Individual and Batch Printing of labels/barcodes for items and storage units.

Printing of machine readable (barcode) and a human readable labels by selecting one at a

time or many at a time. One specific need of this lab is to print labels with unique ID's that have

check digits appended to the ID.

10. Printing of Lists of items and storage units.

Printing lists of items or storage units to a printer or a file (text, xml, pdf, spreadsheet,

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word document).

11. Searching of items and storage units.

Ad-hoc querying (based on attributes like study, cohort, storage unit) of items and storage

units.

12. Browsing of items and storage units.

Predefined queries (based on attributes like study, cohort, storage unit) that allow

browsing of items and storage units.

Blood Study:

Blood study layer consists of retrieval, sorting, aliquoting and shipping of blood

specimens (vials) based on specific study criteria.

Blood Study Functional Requirements:

1. Retrieving: Retrieve vials from BioBank into Pull Boxes per Project.

Vials are retrieved per project based on a list of assays, assay specific parameters (eg.

Participant list, Volume), project specific parameters (eg. Vial priority) and the freezer sorting

rule. The vials retrieved for each participant may contain more volume than requested and may

come from different freezers. The vials are sorted in freezer order by applying the freezer

sorting rule to generate a list of vials per freezer. These freezer pull lists are printed and a

person then physically retrieves (pulls) the vials from the freezers and deposits them into Pull

Boxes in an iterative process. For example if a certain vial is missing in a certain freezer for a

particular participant, the person would then try to look up another vial (location) for that

particular participant and physically pull the new vial from the freezer. This new vial would

then need to be added to the freezer pull list of vials.

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Retrieving Summary:

Parameters:

1. Assay List.

2. Assay specific parameters (eg. Participant list, Volume).

3. Project specific parameters (eg. Vial priority).

Freezer Sorting Rule:

1. For each vial size, sort first by Freezer number (low to high).

2. Then by Rack number (low to high).

3. Then by Box number (low to high).

4. Then by Spot (low to high).

2. Sorting : Sort vials into Sorting/Aliquoting/Storage/Sending boxes per Project.

Vials are sorted per project based on Aliquot parameters, Sorting Box parameters, QC

parameters, Sending Box parameters and the Case Control Sorting Rule. For each sorting step

a sorting list is created and used to transfer the vial from a location in the source box to a

location in the destination box.

Sorting Boxes:

First step in sorting involves separation of vials by sizes (4.5ml, 1.8ml and 0.5ml).

Large vials (4.5ml, 1.8ml) from Pull Boxes are sorted into separate Sorting Boxes (4.5 or 1.8) in

Case Control order by applying the Case Control Sorting Rule. Vials then travel along either

the 4.5 or 1.8 branches.

Aliquot Boxes:

Next the vials from Sorting Boxes are then split (aliquoted) into multiple small child

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vials (0.5ml) and deposited into Aliquot Store Boxes and Aliquot Ship Boxes in Case Control

order and along their branches (4.5 or 1.8). Labels are printed for the Aliquot vials.

Storage Boxes:

Then, small child vials (0.5) from Aliquot Store Boxes from both branches (4.5, 1.8) are

sorted into Storage Boxes and scanned and physically placed back into the BioBank.

Sending Boxes:

Finally, small vials (0.5ml) from Pull Boxes are directly sorted into Sending Boxes.

Other small child vials (0.5ml) from Aliquot Ship Boxes from both branches (4.5, 1.8) are

sorted into Sending Boxes. Additional small quality control vials (0.5ml) are added into the

Sending Boxes. Vials in the Sending Boxes are sorted by assay in Case Control order by

applying the Case Control sorting rule. A shipping list is created and then the Sending Boxes

are shipped to assay laboratories.

Sorting Summary:

Parameters:

1. Aliquot Parameters (eg. Volume, Quantity).

2. Sorting Box Parameters (eg. Capacity, Box Type).

3. QC parameters (eg. Percent, Type, Set size).

4. Sending Box parameter (eg. Fill method).

Case Control Sorting rule:

1. Sort first into Case Control order.

2. Randomize within Case Control sets.

3. Randomize across Case Control sets.

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Sorting Scheme:

Sorting Scheme

4.5, 1.8, 0.5 QC Pull, QC

Boxes

4.5 1.8 Sorting Boxes

0.5

Aliquot Boxes
SE ST SE ST

Send/Store Boxes
ST SE

QC = Quality Control, ST = Store, SE = Send, Numbers = Vial size

3. Storage of Project.

Participant list, Assay list, freezer pull list, Sorting list and Shipping list are stored per

project. Attributes associated with each of the above are also stored.

4. Tracking of Project progress.

Tracking of Project progress through the entire process. From the point of registration of

Assays for the particular project to generating the freezer pull list, sorting lists and shipping list.

5. Changes in Project.

Frequently, after the freezer pull lists are created and the vials are being pulled from the

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freezers, there are changes in the initial supplied Participant list. Changes include addition of

participants or deletion of participants from initial participant list. This necessiates creation of a

new freezer pull list for the added participants within the same project.

6. Integrity checking of Project.

Vials that are present on the freezer pull list of one project should be temporarily reserved

for that project while they are being physically pulled from the freezers. Integrity checking

function of projects avoids such conflicts.

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 LIFECYCLE OF A BLOOD STUDY PROJECT

“Pulling, Aliquotting, Sorting, Adding QCs”

Lifecycle of a Blood Study Project Research Assistant (RA) retrieves cryo vials from freezer, thaws
And makes appropriate size aliquot for sending out for testing
and makes other aliquots to return to storage in repository

“Get In Queue”
Project Manager (PM) adds funded research
project to the appropriate queue “Updating”
RA updates repository
inventory to reflect changes
“Case Control Specs” biospecimen inventory
Investigator provides detailed Project Specifications “Billing”
regarding selection of qualifying participants PM bills
to the Programmer Investigator for cost of
preparation and
“Sending” shipment of samples
RA ships samples to
“Case Control Lists” outside lab for analysis
Following Project Specifications, Programmer with detailed shiplist
makes final list of qualifying participants and
sends ID list to the Study Coordinator (SC)

“Raw Results”
Outside lab sends PM electronic file of
“Tally and Pull Lists” assay results for each ID in shiplist
Using repository tracking software,
SC assesses available volume of sample for
each ID, and prepares pull list of freezer locations
for cryo vial(s) for each participant.
“Final Results”
Programmer evaluates CVs
of imbedded QCs in data set before releasing final
results data set to Investigator for analysis

Schematic kindly provided by Helena Judge-Ellis

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