allotrope framework implementation in the bioanalytical lab

Allotrope Framework implementationin the Bioanalytical Lab

Dr. Gerhard NoelkenAll t B D b Pfi All t Li iAllotrope BoD member, Pfizer Allotrope Liaison

EBF 8th Open Meeting

©2015 Allotrope Foundation

EBF 8th Open Meeting19 November 2015

Allotrope Foundation• Subject Matter Experts

Member CompaniesAbbVieAmgen

BiogenBoehringer Ingelheim

Genentech/RocheGlaxoSmithKline

• Project FundingMember Companies Baxter

BayerBristol‐Myers SquibbEli Lilly

Merck & Co.Pfizer

• Project Management• Legal & Logistical Support

Secretariat

• Legal & Logistical Support

F k D l tProfessional • Framework Development• Technical Leadership

ProfessionalSoftware Firm

• Requirements & SpecificationsPartner Network

ACD/LabsAgilent Biovia

Mettler ToledoPersistentRiffyn

Waters

Erasmus Univ.

• Contributions, PoC ApplicationsBioviaBSSNIDBS

RiffynSartoriusShimadzu

Med CenterUniversity of Southampton

©2015 Allotrope Foundation 2

Mestrelab Research Thermo Scientific

What is Allotrope Creating?p g

Application 1 Application 2

Instrument A toolkit that enables use of the standards &Application 1 Application 2

Metadata

New Instrument

use of the standards & metadata in software

development

Allotrope Foundation FrameworkAllotrope Foundation FrameworkReusable

Metadata repository

Software Components

St d d Open l f f d d b lStandard

File Format

pMetadata

Repository

dat

File format for any technique or instrument

Project Test InstrumentAF 0012354 IR Fingerprinting QC Lab #33B 380 FT‐IR

Standard vocabulary & structure for metadata

.etc

.etc

.etcetc

.etc

.etc

.dat

.tbl.HDF

.raw .csv

.DAML

.LCD

.XMLjd f

AF 0012354 IR Fingerprinting QC Lab #33B 380 FT IRAE0012764 Bulk & Tapped Density ASTM Standard Seive #6AF 12989 NMR Characterization AM500

Tapped & Bulk Density Sieve XXXAF0045674 Caractérisation RMN Nouvelle DRX600AF‐0034558 IR iS10 FT‐IR

.etc.etc

.etc

.etc

.etc

.mzML

.jdx

.irf .pdid.drdd

.asc

.cdf

.frx

.adf AF 0034558 IR iS10 FT IR

Project Test InstrumentAF0012354 IR Fingerprinting 380 FTIR/‐SN/145453AF0012764 Bulk and Tapped Density ASTM Sieve‐SN/3452

With the Metadata Repository


pp y /AF0012989 NMR Characterization AM500‐SN/0034578 AF0013142 Bulk and Tapped Density ASTM Sieve‐SN/09783AF0045674 NMR Characterization DRX600‐SN/10234567AF0034558 IR Fingerprinting iS10 FTIR/‐SN/341980

Allotrope Data Format (ADF)

Contains:Contains:• Method, instrument, sample,

process, result, etc.• Data cube metadata

Allotrope Data Format

Data DescriptionData DescriptionRDF ModelRDF Model

• Data package metadata• …

Data Cubes Data Cubes Universal data containerUniversal data container

Analytical data represented by one- or multidimensional arrays.

Universal data containerUniversal data container

Data Package Data Package

Analytical data represented by arbitrary formats, incl. native i t t f t i df Data Package Data Package

Virtual file system *Virtual file system *instrument formats, images, pdf, video, etc.

Specificall designed to store and HDF5Platform Independent File Format

Specifically designed to store and organize large amounts of numerical data.

©2015 Allotrope Foundation * Use is optional

4

Example: 36‐Month Stability ProtocolMethod, Impurities, Peaks, Decisions, Stability Time Point, Packaging Configuration, Storage

Allotrope Data Format Conditions, Sample Preparation Events, Weights, Concentrations, Specifications, Integration Events, Scientist, Time Stamps,

di il S l iAllAll Metadata & ResultsMetadata & Results Audit Trail, Measurement System, Real‐Time SOP & Compliance Checks

ChromatogramsChromatogramsPressure TracesPressure Traces

Vendor File FormatsVendor File Formats

Enterprise AnalyticsLong‐Term PreservationStability Reports

HDF5

Vendor File FormatsVendor File Formats Regulatory SubmissionsInspections, AuditsData ExchangeHDF5

Platform Independent File Format

Data ExchangeConfidence in Data


Allotrope Taxonomies: An Extensible Metadata ModelMetadata Model

• A library of extensible • Initial versions of 12A library of extensible taxonomies– Uses W3C standards

• Initial versions of 12 analytical techniques already implemented:

– Easy to understand and maintain by SMEs and Vendors

St t b h ti i ti

implemented:– gas chromatography– Karl Fischer

• Start by harvesting existing available concepts– PSI‐MS; IUPAC; RSC Chemical

– liquid chromatography– mass spectrometry

nuclear magnetic resonancePSI MS; IUPAC; RSC Chemical Methods Ontology; Dictionary of weighing terms; AnIML, etc

R d ibl & ffi i

– nuclear magnetic resonance spectroscopy

– thermogravimetric analysis• Reproducible & efficient

collaboration modelLeverages knowledge engineers

– ultra violet spectrometry– cell counter

cell culture analyzer– Leverages knowledge engineers & member company scientists

– 2‐3 weeks to develop initial

– cell culture analyzer– blood gas analysis– balance


version of a new taxonomy – pH6

More Taxonomies Available in 1Q 2016• Instrument Taxonomies

P t i Ch t i ti• Other Taxonomies

IDMP Id tifi ti f M di i l– Protein Characterization– Microplate Reader– Flow Cytometer

– IDMP‐Identification of Medicinal Products

– Extend Process (S88)Flow Cytometer– Protein Purification– Millipore Filtration System

( )– Extend Materials– Extend Equipment

– Differential Scanning Calorimetry (DSC)X R P Diff ti (XRPD)

– Investigation/Study/Analysis– Phase of Development

R t f Ad i i t ti– X‐Ray Power Diffraction (XRPD)– Particle Sizer– Roller Press

– Route of Administration– Product Quality Attributes– Container CategoriesRoller Press

– Tablet Pressing– Tablet Coating

Container Categories– Chemical Reactions

– Dynamic Vapor Sorption (DVS)– solid‐state NMR (ssNMR) Funded by Individual Allotrope

Member


– Infrared Spectroscopy (IR)7Shared with Allotrope Foundation

Allotrope Foundation Taxonomies


The ADF enables a self‐contained documentation of the data & metadata

ProcessStep

Legend

Data & Metadata Interoperability

(Plug & Play)More automated reporting,

Powerful searching

Request Control Inst. Acquire Data

Process Data

Analyze Data

Report & Share

Search & Reuse Data

Plan A l i

Prepare S l

Submit S l

Control Inst. A i D

Process D

Analyze D

Reports R l

Store, ArchiveAnalysis Samples Samples Acquire Data Data Data Results Archive Data

Analytical Sample Prep Instrument Instrument Processed Analyzed Reported St d D tAnalytical Method

Sample Prep Data

Instrument Instruction

Instrument Data

Processed Data

Analyzed Data

Reported Results Stored Data

Standard data file format for data & metadataOutput from one system becomes the input to the next


The APIs enable the use of one vendor agnostic file format

9

Integration Projects Reduce it to Practice

• Divide and conquer: members share the costs and benefits

• Early adoption and acceleration of AF Framework development through delivery of Framework components.development through delivery of Framework components.

• Accelerate vendor adoption via collaboration on delivering specific capabilities through the integration projects

• Ensure the validity of the Framework through real‐worldEnsure the validity of the Framework through real world requirements and implementation.

• Benefit the sponsoring companies in terms of shared development of new functionality & shared experience

• Drive integration of the Framework into the IT/IS Roadmap


Integration ProjectsDevelopmentResearch CommercialM lti l

B

A Small and Large Molecule CMCMultiple types

Elemental ImpuritiesICP‐MS

pH, Weighing, GC, Karl Fischer, TGA, NMR , Cell Density/Viability, Blood Gas Analyzer , Cell Culture Analyzer, Capillary Electrophoresis

C FermentationProcess ControlBioanalyzer

…

D CRO IntegrationHPLC‐UV

E

St t ID P ifi ti

Structure IDHPLC‐MS

D CRO IntegrationHPLC UV

F Structure ID, Purification,In vitro BioanalysisHPLC‐UV/MS

G Assay, PurityHPLC‐UV

I

H Drug Substance Release & Stability

Method ScreeningHPLC‐UV/MS

HPLC‐UVBalance

I Method ScreeningHPLC UV/MS

J LC Data to ADF Converter/AdapterHPLC‐UV


Member non‐GMP GMPInstrument

APN Member PoCs

ADF multipleAPN M b APNM bAF TaxonomiesADF multiple techniques(results only)

APN Member “ELN”

APN Member “SDMS”

Integration Project AGMP Development

AF TaxonomiespHWeighing

TGANMR

LES

WeighingHPLCUVMSGC

NMR Cell Density/ViabilityBlood Gas Analyzer Cell Culture AnalyzerCapillary Electrophoresis

ADF multiple

GCKarl Fischer

Capillary Electrophoresis…

Instruments Data Lake(Hadoop)

ADF multiple techniques(results only)


SSummary

20162015

2016• Framework Development

• Framework used in production• First Public release

2014• Established feasibility through PoCs

Framework Development• Integration at Members

2013

y g• ADF design & due diligence

2013• Initiated software development

and evaluations

2012 Allotrope Foundation


Allotrope Foundation

The Framework will provide Business benefitLess Manual Document Preparation

Improved Data Integrity

Seamless data exchange & with partners & CROsPreparation

• Find data quickly/logically• Eliminate Copy/paste• No more

• Eliminate error due to manual text entry or transcription

partners & CROs• One data file format• One consistent vocabulary• Reduced cost & complexity• No more

Transcription/conversion• Source agnostic

transcription• Complete, consistent, accurate metadata

• Reduced cost & complexity to CROs, CMOs, partnerships

Lower Data Facilitate Regulatory Extracting Knowledge Management Costs

• Interoperability

g yCompliance

• Improved instrument &

g g& Value from Data

• Greatly enhance speed to • Future‐proof against future data migrations

• Reduced technical debt: no

software validation tracking

• Reduced complexity in d i

answer/decision• Remove data silos• Create an ecosystem for

more maintenance of legacy systems

• Improved archiving

system documentation• Simpler to support questions/investigations

innovation• Facilitates data mining & analytics

©2015 Allotrope Foundation 14What are your priorities?

Thank you!

To join or get additional information, contact:

James Vergis, Ph.D.

To join or get additional information, contact:

James Vergis, Ph.D.James Vergis, Ph.D. Science Advisor | Drinker Biddle & Reath LLP1‐202‐230‐5439

James Vergis, Ph.D. Science Advisor | Drinker Biddle & Reath LLP1‐202‐230‐[email protected]@allotrope.org [email protected]@allotrope.org www.allotrope.org


allotrope framework implementation in the bioanalytical lab

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