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Compliance and work efficiency improvements through implementation of a UNIFI Network
Marco Michi
EBF Waters Workshop 15 November 2016
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Outline
Aptuit Overview
Regulated Bioanalysis
Architecture and Software Requirements
UNIFI key features for Regulated Bioanalysis
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Our drug discovery & development solutions
Our extensive experience, considerable capabilities and industry insight mean we are in a position to help meet your drug discovery and development challenges. Wherever you are. Whatever your ambitions.
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Drug Design and Discovery
Integrated Chemistry, Manufacture and Controls
IND Enabling Programs
INDiGO®
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Key aspects for regulated Bioanalysis Over the GLP and GCP requirements and scientific quality the following aspects are very important for the Bioanalysis lab in a CRO:
Analytical throughput without compromising scientific quality
Robust quality control check
Resource optimization
Fast reporting
Raw data handling (electronic for FDA)
Access management
Software Validation
Disaster Recovery
DATA INTEGRITY, Audit trail and full compliance!!! 6
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Main Agencies and Regulatory Guidelines
FDA BMV Guidance, 2001 EMA BMV Guideline, 2012 FDA GLP: 21 cfr 58 OECD GLP ICH M3 (R2) EMA Reflection paper for laboratories that perform the analysis or evaluation of clinical
trial samples (2012) EMA Guideline on the investigation of bioequivalence (2010) FDA CFR 21Part 11 GAMP 5 General Principles of Software Validation; Final Guidance for Industry and FDA Staff Data Integrity and Compliance With CGMP Guidance for Industry (FDA draft) OECD Number 17 (more recent one) Green guidelines are specific for clinical trial support Red guidelines are specific for data integrity and software validation
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General considerations Our Bioanalytical lab produce:
More than 50K results per year
About 500 reports/contributions
9 LC-MS/MS working also overnight
More than 90 methods developed and qualified or validated per year
24 total headcounts 18 active analysts 2 sample managers
Key aspects to define:
PROCESSES
INSTRUMENTS and SOFTWARE
IFRASTRCUTURE
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Main Bioanalytical Access Requirements
Raw data can’t be deleted or modified in any process phase
Modifications should be easily identifiable by reviewers and auditors
Audit should be performed on original raw and processed data (electronic)
Archived data can be accessible only to the Archivist
All these requirements are not easily implemented by means of a desktop installation
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Infrastructure selection Local installation is the simpler, each system is a stand alone system
Manual data transfer or network acquisition
Instruments should be manually synchronized with the last method version
Several files are usually moved/handled manually using windows explorer
Risk for data deletion or corruption
Metadata search is not possible
An higher rating in the Risk assessment profile requires more validation effort
Network installation All LC/MS systems are controlled by a single central software
access management, permissions and method parameters are centralized
Possibility to monitor all instruments from a single user interface
No manual raw data transfer
Data segregation more easy to be implemented
Single central software ensure all the systems behave the same
Metadata search is possible
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Software and instrument selection
Historically the choice was mainly driven by the instrument selection based
on mass spec performance
Today, software are becoming more and more important and for some
applications are more important than some mass spec specifications
For regulated Bioanalysis it is crucial to select a software that
ensure DATA INTEGRITY
minimize
Use the current method version
Avoid accidental deletion of the data.
UNFI network solution was selected to accomplish all these points
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Installed Network System Diagram DL380 3.5GHz x 8 cores, 32GB RAM 1 unit 600GB RAID 1 for OS, DB (Oracle 12) and application 1 unit 3.2 TB RAID 5 for Oracle data 1 unit 3.7 TB RAID 5 for Fast Recovery Area (FRA)
\\itnt06\UNIFI
Win7 64bit, 4GB RAM
i7 Win7 64bit, 8GB RAM, 500GB HDD
Instrument 1
Client PC 1 ( physical / virtual )
LND 1
Client PC 4 ( physical / virtual )
Instrument 2
LND 2 UNIFI Server
File Share
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Disaster Recovery Configuration Strategy:
5 + 1 spare disks are configured for each RAID 5
Operative System and DB application on RAID 1 array
Daily backup on FRA RAID 5 and on external data center
Virtual installation of the system on Cloud Service
Restoring Process:
Data Base (including study data) can be restore from FRA and External Data Center back-ups
Operative system and DB configuration can be restored from Virtualized Installation
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Bioanalytical Process Related to UNIFI Bioanalytical process with UNIFI
Stud
y Se
t Up
Acqu
isitio
nPr
oces
sing
QC
Revi
ewQ
A Au
dit (
if re
quire
d)Ar
chiv
ing
Biolims
Analyst
Print Worklist Sequence
Biolims
AnalystCreate Worklist and
Export in shared area
Worklist Sequence.XLS
UNIFI
Analyst
Import Worklist Sequence
UNIFI
Analyst
Start Acquisition
UNIFI
Analyst
Chromatograms integration
UNIFI
AnalystOpen the Approved report and export
results to s.a.Biolims
Analyst
Import Excel fileResults by 15'
Biolims
Analyst
Apply results code and accept Worklist
Worklist Sequence
ChromatrogramsInfo FileAudit Trail
ChromatrogramsInfo FileAudit Trail
ChromatrogramsInfo FileAudit Trail
UNIFI
Analyst(if Required) Export UNIFI Report in pdf
in s.a.
Have you processed all
Runs?
UNIFI
ReviewerReview
Chromatograms and sign report
Reviewer
Check Study File integrity and send to QA (when required)
UNIFI
AnalystProduce Analysis
Report using approved template
Biolims
ReviewerReview Results and apply QC checked
statusAny issue?
UNIFI
QA
Review electronic data
Any issue?
END
START
Biolims
AnalystCreate the Assay
accordingly to the UNIFI Analysis Meth
UNIFI
Analyst
Create the Analysis Method
UNIFI
Analyst
Create the Project Folder
Reviewer• Review Analytical Data,
BioLims Result code
• Verify the data of the last Signed Report report version in UNIFI are imported in BioLims
• Sign PCS_213
Any issue?
Analyst
Perform the required Corrective
Action
YesYes
Biolims
ReviewerCheck data and mark Study as
Completed
Yes
UNIFI
Analyst
Sign electronically the report
Yes
UNIFI
AnalystChange folder
project status to Off-line
Analyst
Final Review to ensure data
integrity
Analyst
Send paper to ACR and PDF to
electronic device
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UNIFI key features for Regulated Bioanalysis when RAW data are defined as electronic RAW data
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Analysis Method
All method parameters, sample list properties, processing settings, reporting template and historical versions are grouped in a single item called (Analysis Method)
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Analysis Method Comparison
Analysis method are versioned and only the differences between two versions can be displayed and highlighted
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Reporting: highly customizable report template
all analysis data in a single item convertible to .pdf format for long term archiving purpose
Reported data are automatically kept synchronized
No risk to report superseded data
Many report items can be used
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Central Library: Custom or Master libraries
All information including mass spec optimized parameters are available in a central repository
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Central System Monitor
All Mass Spec are under control and estimated time to finish the analysis is reported
All Mass Spec can be remotely controlled and policies for e-mail alerts can be customized
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Central Administrator
Admin features are active based on user profile.
Custom field are highly customizable
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Other useful features Audit trail reasons for change are “intelligent”
Reasons are customizable and many predefined are available
Assay functionalities, system behavior and available features change
depending on the selected type of assay (e.g.: quantify small molecule,
peptide, matrix effect, Tof, metabolite id, MSe etc.)
Possibility to import all .pdf and Office files into the system
LND PC take care of your analysis ensuring access protection
Personal home page to control draft/on-going analysis and report pending
electronic signature is available with alerts when due date is close to expire
Possibility to electronically archive data with one click
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Conclusions Network UNIFI Installation demonstrated to:
Improve compliance and data integrity compared to typical desktop installation
Make the electronic data archiving easier
Make review faster following predefined workflows
Make the data migration to .pdf file for long term archiving purpose faster
Ensure work flexibility
Make software validation simpler
Reduced likelihood of human error
non-compliant actions are limited or inhibited and worming messages are prompted
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