ISIS BioComp & TFR/Tox

• This is a demo about ISIS BioComp and TFR/Tox

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ISIS BioComp

Computing for Bioresearch

Established in 1988

Offices: Murrieta, CaliforniaStockton, New Jersey

ISIS BioComp Presents TFR/Tox

TFR/Tox

• TFR/Tox provides General Toxicology and Reproductive Toxicology in a single integrated system

• TFR/Tox is a client/server system

• TFR/Tox can operate in Windows 95, 98, ME, or Windows NT, 2000

• The database is Oracle

Hardware Requirements

• Workstations should have PC’s with a Pentium processor with at least 32 MB of memory

• A VAX, Digital Alpha, Unix server or Windows NT system, or any other Oracle server system, can be used as the database

• A modem or Internet connection is required for support

Software Requirements

• Oracle Database• SQL*Net v2 or Net8• SQL Plus• SQR (Brio.Report)• pc Anywhere

TFR/Tox Peripherals

• TFR/Tox interfaces with a wide variety of peripherals– Scales (Mettler, Arbor, Ohaus and

Sartorius)– Barcode Readers– BMDS and Avid Animal Identification

Scanners

TFR/Tox Support

• Support is provided by Glenn Koehler located in Stockton, New Jersey

• Glenn originally worked for Exxon Biomedical Sciences and was involved in the daily use and validation of TFR/Tox

• ISIS BioComp can run and evaluate remote systems with the use of a modem and software such as pc Anywhere

TFR/Tox Users

• Bristol-Myers Squibb• Exxon Mobil Biomedical • Aventis• Sanofi-Synthelabo• Glaxo SmithKline• Wyeth Ayerst Research

Why TFR/Tox?

• May solve your present problems

- It’s flexible and configurable

- Very user-friendly

- Graphical interface

- Emphasizes reliability and ease of use

- Data is highly usable

Why TFR/Tox?

• It will save time and money

• It’s completed, validated, documented

and in everyday use

• It may relieve your present system’s

major deficiencies

Why ISIS BioComp?

• Preclinical Software is our only

business

• Exceptional technical support

• Capability and Integrity

Important Concepts - TFR/Tox

• Scheduling • Phases & Phase Triggers• Subgroups• Global Glossaries• Lookup Tables• Data Collection Order Lists• Supervisor Approval• Blind Accession Numbers• Study Templates

Scheduling

• Animals are scheduled for data collection (body weights, clinical

signs, dosing, etc.) automatically each night

• A list of observations can be reviewed at the beginning of each day

• The list is updated as the tasks are completed during the day

Scheduling

This screen can be reviewed to see what is scheduled for this study today. It will be filled in by the system as data collection exams are started and completed.

Scheduling of Exams

• Examinations can be scheduled for phase day, study day, phase week or study week

• Schedule Types include– Absolute Day (e.g., July 4, 1998)– Discrete Day (e.g., Day 19 of Gestation)– Frequency (e.g., every 3 days)– Days of week (e.g., Monday & Friday)– By Parameter (e.g., following dosing)

Scheduling

Observations can be scheduled for animals in specific phases.

Observations are scheduled by what phase the animal is in at the time of scheduling.

Scheduling

This observation will be scheduled starting on Day 1, a frequency of every day, no tolerance and for the duration of the study.

Phases

• An animal is assigned to a phase at the start of study

• All phases can start on either Day 0 or Day 1 for scheduling purposes

• Triggers are set to automatically shift an animal into another phase

• Manual phase shifting is also available

Scheduling

This screen lists the available phases. Any number in the Duration (Days) column changes the In Use Column from "n" to "Y" indicating it is available for the study.

Phase Triggers

• Animals can be phase shifted manually by the user at anytime during the study

• Triggers can be defined to result in automatic phase shifts

Scheduling

Animals can be automatically triggered from one phase to another. For example, both "In Situ Plug Present" and "Sperm Present" trigger a female from Pregestation to Gestation.

Subgroups

• All animals can be scheduled for an examination or select animals can be assigned to subgroups

• Animals can be assigned to a subgroup if only select animals will be scheduled for an examination – Satellite Animals– Interim Sacrifice– Blood Collection

Scheduling

Subgroups are used to schedule a subset of animals for a specific observation (e.g., Blood Collection).

Scheduling

Clicking with the mouse or highlighting and pressing <Enter> or the Spacebar will select or deselect the animal.

The dashed arrow indicates that an animal has been assigned to a subgroup.

Animals can be assigned to subgroups either manually or randomly.

Global Glossaries

• Topography, morphology and descriptor glossaries are user-defined

• Glossary terms can be defined for up to five levels

• Level 1 - Topographies - are based upon body systems : nervous, urinary cardiovascular, digestive, etc.

Scheduling

Topographies can be identified as being sex specific (e.g., Female Reproductive System or Male Reproductive System)

This is the Global Topography Glossary. The first level (Level 1) is based on body systems. Each topography can have up to five different levels.

The number in the # MEMB column indicates how many entries exist at the next lower level.

Scheduling

This shows the Level 2 Glossary items for the female reproductive system.

Scheduling

This shows the Level 2 Glossary items for the female reproductive system.

This is the Global Morphology Glossary. The first level (Level 1) is based on a specific examination. Each morphology can have up to five levels.

Scheduling

This shows the Level 2 Glossary items for the female reproductive system.

Morphologies can be classified as either malformations or variations. An optional description of the morphology can also be entered.

This screen shows the Level 2 glossary items for the Fetal Gross Exam.

Lookup Tables

• Defined by user

• Popup tables used in study configuration and data collection

• Selection with mouse or by highlighting and pressing enter

• Lookup tables can be multiple selection

Scheduling

Lookup Tables are defined or altered in Global Management.

Lookup Tables are a list of popup entries which can be user defined.

Scheduling

These are the entries for the Audit Reason Lookup Table. They are user defined. New reasons can by added by the User in Global Management.

Data Collection Order Lists

• Random generated lists of animal

numbers for any data collection

endpoint

• Can be generated anytime manually

• Can be generated automatically at time

of data collection

Scheduling

Data Collection Order Lists are random lists of animals presented to the user at the time of data collection. These lists can be generated at the time the study is set up or at the time of data collection

Scheduling

This is a random list of animals generated for Blood Collection.

Password Protection

• Protection is hierarchical

• Global Authority is necessary to access any part of the system

• Access can be authorized on a study and/or an examination basis

• In team functions, a password is required from each team member

• Complies with 21CFR11 regulations

Scheduling

Users must be initially identified to the system in Global Management. This is a list of users with their User IDs, Passwords, initials and their Module Authority.

Scheduling

Module authority can be assigned to a specific user. The arrows indicate which functions the user can perform.

Audit Trail

• Once a study is marked active, an audit record is required for any change to the data

• Audit Trail retains the original data and the change, along with who made it, when it was made (date/time) and a reason for the change

• An audit log can be printed out for each study

This audit log lookup table automatically pops up when a change is made. The actual change, who made the change, why the change was made, and the date and time are all recorded in the audit log. A reason can be typed in via the keyboard if an appropriate selection is not available.

Scale Calibration

• Scales can be calibrated prior to and at the completion of an examination that uses scales

• Up to six calibration weights can be defined

• Scales can be divided into three classes

Scheduling

The scale can be calibrated using up to six (6) calibration weights. A log is maintained of the calibration results. Scales classes are used for identifying scales with different weight ranges (e.g., Scale Class 1 for body weights and Scale Class 2 for small organ weights).

Supervisor Approval

• Data Collection Sessions can be approved by a supervisor

• Specific morphologies can be approved by a supervisor

• Data can be approved at the time it is collected or at a later date

Scheduling

The data collection can be reviewed and approved by the supervisor at the end of the data collection session or at a later date at the discretion of the supervisor.

Scheduling

Specific morphologies can also require Supervisor Approval at the discretion of the User.

Accession Numbers

• Accession numbers are used to display and access study animals for exams in a "blind" mode

• Operator does not know the dose groupassociated with an individual animal during exam data collection

• The user can either manually assign accession numbers for the animals, or request that accession numbers be randomly assigned by the system

Scheduling

Accession numbers are blind numbers used in data collection without reference to group or dose level. Accession numbers can be assigned manually or randomly by the system. These have been assigned randomly by the system.

Study Templates

• Templates can be set up for various types of studies

• Templates can be quickly copied when setting up a new study

• Templates contain all study information except animal identification numbers

• After animal allocation, study setup is complete

Help Screens

• Context-sensitive help is available at any point in TFR/Tox

• The user may request either a general help screen or a field-specific help

• The user can customize the help information

Scheduling

This is an example of a General Help Screen relating to the Study Selection screen. It is invoked by pressing the F1 key.

Scheduling

This is an example of a Specific Field Help Screen relating to the Study Selection screen. It is invoked by pressing the F2 key.

TFR/Tox

• TFR/Tox can be used for General

Toxicology Studies

• TFR/Tox can be used for Reproductive

Toxicology studies

TFR/Tox

• TFR/Tox can be used for all kinds of general toxicology studies

– Dose Range Finding– Acute, Subacute and Subchronic– Chronic Oncogenicity/Carcinogenicity– Neurotoxicology– Acute Eye Irritation– Draize Skin Test

Toxicology Examinations

• Food and Water Consumption• Clinical Signs• Dosing• Post Dose Observations• Veterinary Examination• Body Weights• Physical Observations• Ophthalmic Examination• Mortality Check

TFR/Repro

• TFR/Tox can be used for Reproductive Toxicology Studies– Fertility Study (Males and/or females)– Developmental Study– Perinatal and Postnatal Study (With or

without Behavior)– Multigenerational Study

Reproductive Examinations

• C-Section Observations• Fetal Gross, Visceral & Skeletal• Sperm Toxicity Evaluation• Estrous Cycle• Mating Observations• Littering Observations• Pup Maze• Pup Viability/Developmental

Starting TFR/Tox

• TFR/Tox is started from the Start menu, or via the TFR/Tox icon.

Scheduling

This is the initial Logon screen for TFR/Tox. It is the first screen the user sees when he/she logs onto TFR/Tox. The user enters his Password or both his User ID and Password depending on how it is configured in Global Management.

Study Configuration

• Studies are set up as either General Toxicology or Reproductive Toxicology studies

• A short protocol is completed• Groups are defined• Animals are requested and allocated to

study• Study is marked active which starts audit trail• Schedule is updated and data collection can

begin

Interview Screen is completed in a systemized order to configure a new study. A "Yes" in the Required Column indicates that the activity is required and must be completed by the user to configure the study.

An "E" in the Status Column indicates that the User has entered this activity.

Scheduling

The Study Title, Study Type, Start Date and Species are required. The remaining entries are optional.

An "E" in the Status Column indicates that the User has entered this activity.

A short protocol is completed. Many of the entries can be completed by making a selection from a lookup table.

Scheduling

Animals can be allocated 1) directly into the study, 2) into a quarantine pool within the existing study or 3) into a quarantine pool. Staggered start dates are supported. Each individual animal is on its own schedule.

Scheduling

The schedule is normally generated automatically each night. The schedule can also be updated from this screen.

Scheduling

The data collection observations can be reviewed from this screen. This screen is automatically updated as the data are collected.

Data Collection

• All data collection endpoints are automatically scheduled daily

• Unscheduled data can be collected with an audit reason

• Individual examinations are selected from a data collection screen

The only activities that the User will see are what he/she has been globally approved to perform.

The white function bar at the top of the screen contains various functions. They can be selected by clicking on them with the mouse or by pressing a 'Hot Key' (Alt key and capitalized red letter).

Select the desired Activity - Data Collection if data are to be collected

The animals scheduled for a specific examination can be reviewed with the function "show Scheduled animals.” The mode of data collection includes Group/Sex/Phase, Sex/Phase and Phase.

Select the desired examination for Data Collection. The mode of data collection can be changed by the user. The default was set up in Study Management.

Body Weights/Feeder Weights

• Weights can be entered via the keyboard or captured automatically if scales are attached

• Fresh feeder weights and used feeder weights can be collected at the same time

Scheduling

If Teams are used for data collection exams, Team Members must individually enter their Password. Once the password has been entered, the name of the individual will show up as above.

Body weights and fresh and used feeder weights can be collected from this screen. They can be entered manually from the keyboard or automatically if connected to a scale. The blue box at the top can show up to five (5) previously collected body weights and the dates they were collected.

A mask (^^^.^) can be utilized to specify the number of decimal places if the data are recorded manually. The mask for the body weights shown on this screen consists of three digits, a decimal point and a fourth digit.

Organ Weights

• Organ weights are specific to the sex of the animal

• Organ weights can be entered via the keyboard or automatically if connected to the scale

• Paired organs can be weighed together or separate

• Organs can be weighed fresh or fixed• Organ weights can be excluded from statistics

Scheduling

Organs can be weighed fresh or fixed, paired or separate, and can be excluded from statistics.

A Comment can be made regarding an organ weight.

A Comment can be made regarding an organ weight. If a comment is made, an asterisk will appear in the COMMENT column.

Clinical Signs

• Clinical signs are derived from a global glossary with up to 5 levels

• Previous or “open” signs must be confirmed or ended prior to

addition of new signs

• Default can be applied to mark all animals as "Not Remarkable"

Scheduling

This clinical sign must be either confirmed or ended before additional clinical signs can be entered for this animal.

A new clinical sign has been added and will show up as an 'Open Sign' the next time Clinical Signs are performed.

Extended In-life Clinical Exam

• All of these exams can be collected on the same screen– Body Weights– Fresh and Used Feeder Weights– Clinical Signs– Dosing

This is the left side of the screen for the Extended In-life Exam.

This is the right side of the screen for the Extended In-life Exam.

Dosing

Dose volumes are calculated automatically from the most

recently scheduled body weight or from a specific day specified by the user (e.g., Day 0 Gestation)

• Dosing can be marked as completed from the computer or from a paper record

Scheduling

Animals can be marked as 'Dosed' from this computer screen or from a paper dosing record. The animals in this study are being dosed with two different compounds.

Post Dose Exam

• The Post Dose Exam is scheduled By Parameter and can not be performed until after dosing is completed.

• A number of replicates can be scheduled for the the Post Dose Exam.

• If the clinical sign is still present at the last replicate a new replicate is automatically scheduled

Scheduling

This Post Dose exam is scheduled ‘By Parameter’ and includes three (3) replicates. Animals must be dosed before the Post Dose Exam can be performed. Observations can be collected outside of the specified times, but the User will be warned by the system.

Special Examinations

• TFR/Tox can be used for speciallydesigned exams such as the Acute

Eye Irritation or Draize Skin Test.

• Morphologies are created by the user.

Scheduling

This screen is utilized for the Draize Skin Examination. The blue screen at the top shows up to five (5) previous observations with the most recent at the top.

These morphologies have been defined by the User.

Scheduling

This screen is utilized for the Acute Eye Irritation Examination.

Selection of Swelling, Discharge, Injection, Opacity or Involvement will invoke a lookup table with user-defined entries.

Scheduling

The blue screen at the top shows up to five (5) previous

observations with the most recent at the top.

Selection of Swelling, Discharge, Injection, Opacity or Involvement will invoke a lookup table with user-defined entries.

These morphologies have been defined by the User.

Mating Exam

• Male animals can be assigned to female animals manually, sequentially or

randomly.

• More than one female can be assigned to the same male animal.

• Male animals can be replaced with another male.

Scheduling

This exam is utilized to mark animals pregnant based upon the presence of an intact vaginal plug or the presence of sperm in the vaginal smear.

Scheduling

Marking an animal as 'Sperm Present' or 'In Situ Plug Present' will automatically phase shift her from Pregestation to Gestation.

C-Section Examination

• Marking an animal as gravid automatically schedules fetal examination parameters

• Implant observations can be collected and fetuses can be randomly or manually assigned to fetal external, fetal visceral or fetal skeletal examination

Scheduling

A Date and Time Stamp is recorded when an animal scheduled for C-Section is marked 'Gravid.’ The Date and Time Stamp indicates that the animal will be phase shifted from Gestation to Fetal Evaluation.

Various parameters are collected for C-sected animals. Fetuses can be randomized for the fetal exams: fetal external, fetal visceral and fetal skeletal examinations.

The double hatch marks indicate the location of the cervix.

Scheduling

A morphology identified in the Fetal External Examination can be confirmed in the Fetal Visceral Exam.

Littering Examination

• Marking an animal as Delivered automatically phase shifts the

animal from Gestation to Lactation.

Scheduling

Selection can be made by clicking with the mouse on the desired selection or by highlighting the desired selection and pressing <Enter>.

The number of live pups, dead pups, etc. is completed on this screen.

Once the status is completed for each pup, the pups can be assigned identification numbers from this screen and automatically culled.

Report Generation

• TFR/Tox includes over 125 reports in these categories: Global, Study Management, Scheduling, Drug and Diet, Individual Animal, Teratology, Pup, Group Summary, etc.

• More than 125 reports are available; runtime options offer greater flexibility

• Reports can be generated at any time and can be viewed on the screen or printed

Scheduling

The specific type of report can be selected from this screen. More than one report can be selected. Although more than one report can be selected, reports must be generated individually.

The dashed arrow indicates selection of the report.

Scheduling

TFR/Tox does not perform statistics. However, it does calculate means and

standard deviations, and the data can be exported to a program such as SAS for performing statistics.

The report can be viewed from this screen or printed.

Summary

• TFR provides General Toxicology and Reproductive Toxicology in a single integrated system

• TFR/Tox is complete, validated, documented and in everyday use

• It's flexible, configurable and user-friendly

• Oracle database is easily read by SAS

TFR/Tox

• Thank you for viewing this demo of TFR/Tox.

• If you have questions or need additional information, please call (909) 677-2446, or email sales@isisbio.com

• Or view our website at www.isisbio.com

• To end this demo, press the ESC key