caTissue 2.0 Enhanced Specimen Event Tracking and Standard Operating Procedures Use Cases and UI Mockups

Assumptions SOPs are a series of defined procedures that dictate how to procure or process biospecimens As a result of performing an SOP, a biospecimen experiences “events” in its “lifecycle” A specimen may experience events that either deviate from the intended SOP or are completely unanticipated In the process of performing an SOP on a specimen, a new (derivative) specimen may be created Some events or SOPs may occur on a ‘specimen’ before it is instantiated in the system

Assumptions For purposes of quality assurance, tracking a collective set of specimen events is more relevant than the SOP that they compose SOPs and events are not required By default, every CP should have a minimal SOP which includes a single collection event and received event (as is currently true in caTissue 1.2) 3

Assumptions At the level of the SCG, an SOP may define how one primary parent specimen is collected and processed to create all derivative and aliquot specimens, and may also specify how such derivatives are processed by their own SOPs. 4

SOP Example Blood processing SOP

Lab Implementation CP Based View (Specimen Entry) SOP Based View (Event Entry) SOP A Collection Event A PT 1 CP #1 Centrifuge Lyse Freeze Collection Event A Aliquot Freeze PT 2 CP #2 SOP B Centrifuge Freeze Collection Event B PT 3 CP #2 SOP C 6

Proposed Functionality Two major use cases are supported: Create an SOP consisting of a series of specimen events and associate the SOP with an individual specimen requirement or collection protocol event. Use defined SOPs to record associated events after specimen collection/creation. 7

Admin SOP Use Cases Add/Edit Event Templates Super Admin Add/Edit SOPs having series of Events Associate SOP to Specimen Requirements Site Admin Associate SOPs to CP events

Supervisor SOP Use Cases Enter SOP data based on CP for SCGs Enter SOP data based on CP for Specimens Supervisor Add Events data to many specimens View SOP data for individual SCGs View SOP data for individual Specimen

SOP Example Blood processing SOP 10

SOP1 & SOP2 split into events SOP1: Blood Collection SOP2: Cell Pellets Creation EVENT : Spun Speed - 3000 rpm Duration - 5 min Temperature - Equipment - clinical centrifuge EVENT: Collection Container - EDTA vacutainer EVENT : Isolate buffy coat Description : Remove the plasma and recover buffy .. EVENT : Lyse RBC Volume of lysis solution - 5 EVENT : Resuspension Solution - PBS Volume of PBS – 5 ml Description: Add appropriate volume of PBS to have 10-20 million cells per ml of PBS. Using a disposable pipette, gently resuspend white cells by pipetting up and down several times. EVENT : Incubation Duration - 10 min Temperature - room EVENT : Spun Speed - 3000 rpm Duration - 5 min Temperature - Equipment - clinical centrifuge EVENT : Aliquot Container - Liquid Biohazard Container Description: Aliquot equal amounts (approximately 1 ml /tube) of the cell suspension into 1.5 ml tubes

SOP3 SOP3: Frozen Cell Pellet Processing EVENT : Spun Speed - 3000 rpm Duration - 5 min Temperature – 4 C Equipment - TOMY micro centrifuge EVENT : Remove Supernatant Description : Completely remove supernatant from cell pellet with a micropipette. Do not disturb cell pellet. EVENT : Freeze Freezing medium - LN2 or in a dry ice/alcohol bath Duration – 15 Temperature - -20 C Description - Submerge only the bottom half of the tube in liquid nitrogen- DO NOT COMPLETELY IMMERSE THE TUBE. EVENT : Freeze Medium - LN2

SOP Admin Tasks

Admin -> Add Event Template Event Name Event Template Package File Browse Spun Event Upload Package contains zip of Model XMI, Permissible Value XMLs, and Form XML

Admin – Add SOP SOP Name Upload XML file Blood Collection SOP Browse Save Set Defaults and Save Blood Collection SOP SOP Name Upload XML file Browse

Admin – Associate one or more SOPs with a CP event Add all SOPs that result in creation of any specimen (or specimen requirement) collected under this CPE/SCG. Select the SOP (i.e. the event under that SOP) that resulted in the creation of each parent under its specimen requirement. These are the SOPs that will be expected to be performed on specimens collected at this time point in the CP

Admin – Associate SOP to Specimen Requirement Specimen Creation Event Event under an OP used to create the specimen Plasma+PBL SOP for additional processing steps that creates derivatives Freeze Isolate Buffy

Admin – Associate SOP to Specimen Requirement Specimen Creation Event Creation is always an event. Processing is an SOP.

SOP Example association within CP Action: Blood Collection Collection Protocol SOP: Frozen Cell Pellet Processing CP Event Specimen Requirement: Whole Blood Specimen Requirement: Derivative – Cell Pellet Specimen Requirement: Aliquots- Frozen Cell Pellet SOP: Cell Pellets Creation Specimen Creation Processing SOPs: Blood Collection Specimen Requirement: Derivative – Plasma Action: Resuspension Action: Aliquot plasma Action: Aliquot Specimen Creation

Supervisor -> SOP-based specimen event data entry Dashboard for SCG SOP data entry Specimen Collection Group Specimen SOP Blood Isolation CP Title PPI Participant Name SCG Name Collection Time Point CP1 123 Smith, John CP1_SCG1 Initial Diagnosis 124 Smith, Harry CP1_SCG2 125 Doe, John CP1_SCG3 Enter SOP Data In this view, user selects a specific SOP and then can apply / enter all specimen event data for instantiated specimens associated with that SOP, across any CP, at the level of the SCG

Supervisor -> SOP-based specimen event data entry Dashboard for Specimen SOP data entry Specimen Collection Group Specimen SOP Frozen Cell Pellet Processing CP Title PPI Participant Name SCG Name Collection Time Point Specimen Label Specimen Type CP1 123 Smith, John CP1_SCG1 Initial Diagnosis 101231_1 Frozen Cell Pellet 101231_2 101231_3 CP2 101232_1 Enter SOP Data In this view, user selects a specific SOP and then can apply / enter all specimen event data for instantiated specimens associated with that SOP, across any CP, at the level of the individual specimen

Supervisor-> Specimen Event data entry for Specimen based on SOP SOP Label Frozen Cell Pellet Processing Event performed Save Back to Dashboard

Supervisor-> Add SOP/Events data to groups of specimens 45678900, 45679041, 45679041_2,45679041_3, 45679041_5, 45679041_6, 45679041_6, 45679041_7 Use can add a series of defined events (SOP) or individual events to a group of specimens Event performed Attributes of the single event or (in this case) series of events (SOP) are applied to all specimens in the list Save

Remove current events from SCG page

Supervisor-> View SOP Data for individual SCG Blood Isolation SOP Collection Event

Supervisor-> View Events for individual specimens