e-raw data and e-archive in rbmspa - rtc eventi/presentazione-enriettoi.pdf · gxp& electronic...

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Dott.ssa Ilaria EnriettoRBM SpA – Merck BiopharmaMarch 21st 2016

GxP & Electronic Archive Round Table

E-RAW DATA AND E-ARCHIVE IN RBM SPA

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HOW THE PROGRESS TOUCHED OUR TECHNOLOGIES AND ABOVE ALL OUR MINDSET

E-raw data and e-archive in RBM SpA | 21.03.2016

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HOW THE PROGRESS TOUCHED OUR TECHNOLOGIES AND ABOVE ALL OUR MINDSET

From theory to practice: our experience in using an HPLC-UV/VIS system

Moving from paper-based to electronic data

The Ivrea Test Facility paperless project


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AGIT GUIDELINES

PIC/SGUIDELINE

ELECTRONIC DATA DEFINITIONS

MHRAGUIDELINE


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ELECTRONIC DATA DEFINITIONS

Electronic record: All original laboratory recordsand documentation, including data directly enteredinto a computer through an instrument interface,which are the results of original observations andactivities in a study and which are necessary for thereconstruction and evaluation of the report of thatstudy.

Metadata: Data that describe the attributes of otherdata. Most commonly these are data that describethe structure, data elements, inter-relationships andother characteristics of electronic records.

OECD GLP AdvisoryDocument n. 15

Establishment andControl of Archivesthat Operate inCompliance with thePrinciples of GLP


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COMPLIANCE FRAMEWORK

21 CFR Part 11

GAMP 5

Annex 11

PIC/S GUIDELINE

AGIT GLP GUIDELINES

GLP OECD Advisory

Document n.10 CS

FDA

MHRA


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OUR EXAMPLE IN USING AN HPLC-UV/VIS SYSTEM

2010: HPLC used in the Formulation Department in order to perform test itemconcentration analysis, formulation stability and homogeneity studies,validation of analytical methods for quantitative and qualitative analyses

2016: the scope is the same as in the past

WHAT HAS BEEN CHANGED?

We will not underline technologic changes in the system, but we will focus on main changes of its usage and data definition/management


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2010:

The system we are referring to is an HPLC system with a ChemStation management software which allows dataacquisition and basic data evaluations using modules for method and run controls, data analysis module for elaboratingacquired data and report layout module. The HPLC system has 2 different accesses for operator (access for performingthe analysis) and manager (access for performing, reviewing, elaborating and reporting results) according to thedifferent required privilegies. Raw-data and metadata are all locally and temporally stored in the systems itself. There isNO electronic archive in place, the capability of the internal memory is low.

All raw-data considering chromatograms, metadata related to set up/calibration/audit trail, derived data from peackintegrations or elaborations performed in excel file sheets are printed and inserted in the paper study folder


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2016:

The system we are reffering to is OpenLAB CDS ChemStation Edition which provides tools for HPLC dataacquisition, analysis and interpretation monitoring instrument parameters, creating the defined methods,generating and printing (if needed) reports and exporting data to the archived system.

As in workstation or networked workstation configurations, the instrument configuration dialog runs on the local PC.A central data storage system can hold all kinds of electronic data independent of any proprietary data formats.



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2016:WHAT HAS BEEN CHANGED THANKS TO THE ADVANCED TECHNOLOGIES

� Raw data are stored together in the OpenLAB Data Store (centralized data management) partition withalso all metadata including sample information, data analysis method, chromatographic signals,instrument conditions and above all the audit trail.

� All ChemStation methods, sequence templates, report templates, and data files (sequences and singleruns) are uploaded to the file share partition of the virtual server which is identified as GxP Archive.Data can later downloaded back into the ChemStation if required.

� With Secure Workstation for OpenLAB CDS ChemStation Edition ChemStation and Data Store are installedtogether on a single workstation computer.

AUDIT TRAIL � The transactions that occur during the analysis, including accesses, changes,

any errors and the instrument conditions (such as flow, temperature, pressure and solventcomposition for liquid chromatographs) from the start to the end of the analysis are alwaysrecorded and then extracted with every data file. The file includes a revisioning scheme thatindicates if data has been reprocessed. This is an uneditable binary format that ensures theoriginality of the results.



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2016: LOOKING CAREFULLY AT THE AUDIT TRAIL

«Audit Trails need to be availabe and convertible to ahuman readible form and regularly reviewed. Eachchange in the audit trail most not obscure the origianlentry. It should be possible to reconstruct all data beforea change/deletion based on the time stamp of thechange/deletion, the name of the person executing thechange/deletion and the rationale for thechange/deletion. Process owners (GLP SD, heald ofdepartment) or users (analysts) should not be autorisedt change audit trail setting. A system should be in placethat ensures the periodic review of the audit trail systemand the recorded information � GLP QA personnelshould be involved in the review process».

OECD GLP Draft Advisory Document on the Application of the GLP Principles to Computerised Systems



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ACCESSES AND PRIVILEGIES IN THE WORKSTATION

UNIQUE COMBINATION BETWEEN

USERNAME AND PASSWORD FOR EACH EMPLOYEE

Defined rules for psw complexity

Expiry timeframe

Auto log-ff and 3

tentatives max

Administrator

Supervisor

Analyst



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DISASTER RECOVERY PLAN AND BUSINESS CONTINUITY PLAN

All data (primary data – derived data – metadata – audit trail in the original form and in PDF) whichhave been automatically saved after every step on the Workstation itself, are backupped automaticallyeveryday on a dedicated partition of the GxP file share automatically, used as backup folder.

The file shares are controlled accesses partitions where ONLY authorized personnel can have definedpermissions (read or write permission). All permissions list can be checked immediatly by the applicationsor on the server logbooks.

If necessary, data can be retrieved by the backup folder.



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DATA MANAGEMENT

Using a dedicated copy script, after every acquisition the result set containing all data (primary data, derived data,metadata, audit trail in the original form and in PDF) is automatically saved on the server (GxP file share Archive)in the dedicated Data Management folder.

Each folder is identified as «Name of the server / Data / Instrument ID / QUALITY STANDARD / Study Number».

All elaborations (integration, quantification, review, recalculation, elaborations performed on validated Excel files) arealso trackable and saved on the server.

Draft GLP OECD Advisory Doc. on CS


«Raw data: all original laboratory records and documentation, includingdata directly entered into a computer through an instrument interface,which are the results of the original observations and activities in astudy and which are necessary for the reconstruction and evaluation ofthe report of a study.

Derived data depend of raw data (e.g. Final concentrations ascalculated by a spreadsheet, result tables as summarized by a LIMS,written observations and conclusions)».


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DATA APPROVAL AND QA AUDIT

Final draft data (primary data – derived data – metadata – audit trail in the original form and in PDF)after having been consolidated and approved on Chemstation by the Administrator, are completely«frozen» in the system and then they are manually saved by e-archivist on a dedicated subfolder on theserver partition for QA audit related to the draft study report and corresponding data.

WHO WHAT

WHEN WHY

AU

DIT

TR

AIL I

NFO

QA



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DATA ARCHIVING

After QA audit and study report signature, the Study Director is responsible of granting the archive of the studyconsidering either paper and electronic data. Both processes are managed in parallel by the Archivist and e-Archivist.

Final data (primary data – derived data – metadata – audit trail in the original form and in PDF) are archived by e-archiviston a dedicated folder on the server partition which is identified according to the following folder path: «Name of the server –ARCHIVE – Instrument ID – QUALITY STANDARD – Study Number»

E- ARCHIVIST is the only one with writing access to the folder, just for the time of trasferring the data in the archivedfolder.When the study has been electronically archived, the e-archivist signs a dedicated paper Archive History report that has tobe sent to Study Director for confirmation and then sent to the GxP paper-archive for tracking all types ofdocuments/data/specimens archived for that study.

Every change on the archived folder is detectable by the internal audit trail of the folder itself, where all entries/changesare recorded. All other approved accesses can only have «read» permission.

The study can be de-archived ONLY if the requests comes from TFM (e.g. For HA Inspectors requests) and only havingrecorded TFM de-archiviation approval on a dedicated form sent via mail.



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AGIT GUIDELINES FOR THE ARCHIVING OF ELECTRONIC RAW DATA

INTEGRITY OF ARCHIVED ELECTRONIC RAW DATA

AVAILABILITY OF ELECTRONIC RAW DATA

LONG TERM ARCHIVING



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THE ROLE OF THE QA IN THE ARCHIVING PROCESS

QA audits all aspect of archiving

Audit to archiving procedure

Roles and responsibilities

and relative personnel access

Study archiving process and

archived studies

Electronic archives and IT Infrastructure



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THE ROLE OF THE QA IN THE ARCHIVING PROCESS

TRAINING

•Specific technical training in order to letthe auditor understand CS functionalitiesand data management

ACCESS

•QA with read access to all systemscointaining electronic raw data

UPDATES

•Be always «future oriented» in order tofollow innovations



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BACKUP AND RESTORE OF THE SERVERS

Server backups are managed according to local SOP everyday and automatically.

QUALIFIED INFRASTRUCTURE composed either by physical servers and virtual servers.

The virtualization platform is composed by a NETAPP storage system composed by 2 physical units. The firstNETAPP which includes virtual servers (containing also GxP File Server defined as GxP electronic Archive) isbackuped LOCALLY (SNAPVAULT) on the second NETAPP and, for Site specific disaster recovery plan and inagreement with Global Corporate Policies, the second NETAPP is replicated (SNAPMIRROR for files) to theDatacenter of the Main HUB of our Company.

Accesses to the Backup systems are only ALLOWED to IT local personnel.

Data restore (e.g. for local data deletion) can be asked to local ITonly following a procedurised process which grant the traceabilityof each step, also for the restore one.

Server restore test have been performed in the OQ phase of thevalidation process and repeated and tested during periodic review.



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QUALIFIED INFRASTRUCTURE DESIGN

The RBM Infrastructure is composed by:

� Network (VLAN, racks and switches, routers,firewalls, Wi-Fi access points)

� Servers (physical and virtual)

� Clients (Merck Biopharma standard clients and non-standard clients)

� Printers

� Server Room with Anti-fire system, environmentalconditioning control system, access control systemand intrusion prevention system with alarms

� IT Infrastructure software tools (e.g. Jenny Portal,LANDesk Management Suite, PushPortal, SpectrumOneClick for Infrastructure)



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THE PROCESS WE ARE WORKING ON, SHOULD GRANT:


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DATA INTEGRITY CONCEPT

Data Integrity means the degree to which acollection of DATA is complete, consistent andaccurate:

� Good Documentation Practices are followed;

� Content of Data is trustworthy and reliable(data is valid).



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DATA INTEGRITY CONCEPT

MHRA:� All phases in the life of data from initial generation and recording through processing

(including transformation or migration), use, data retention, archive / retrieval anddestruction(MHRA GMP Data Integrity Definitions and Guidance for Industry; March 2015)

� Data (paper and electronic) created /documented following GoodDocumentation Practice?

� Processes / Systems in place to ensuredata integrity across the entire Data LifeCycle?

� Quality Management & Governance inplace to promote Data Integrity?



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HOW TO ASSURE DATA INTEGRITY

Key questions to consider when defining riskmitigation strategies:

� Do I have all my data?

� Am I reviewing all my data?

� Has my data been objectively processed?

� Am I reporting all my data?



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THE WORK OF QA IN DATA INTEGRITY PERSPECTIVE

� Do we include data integrity aspects in our audits?

� Do we review the right data (and metadata) when preparing for /performing audits?

� Are our auditors adequately trained on the electronic systems to allow aneffective review of original data?

� Do we assess quality management systems of vendors for data integrityaspects when performing vendor audits?

� Are data integrity risks reflected in our risk assessment tools?

� Do we include data integrity aspects when preparing for inspections?

� Do we prepare auditees for the methodologies used in data integrityinspections?



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WHAT IS NEXT? PAPERLESS PROJECT!

ELN implementation, mandatory for Corporate Policies in non-regulated environment and corresponding studies/activities

ELECTRONIC NOTEBOOK

Supportive documents to study management (study folders) will no more exist in paper but will be managed by a centralized repository where all supportive

info will be documented/scanned.

As soon as validation will be completely GxP compliant, ELN project will be extended to GLP environment � dedicated implementation plan will be presented to HA


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WHAT IS NEXT?


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THANKS FOR YOUR ATTENTION!


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