of Biologics Using LC/MS in Compliant Laboratories

Transcription

1 Demonstrating Comparability and Consistency of Biologics Using LC/MS in Compliant Laboratories Patrick Boyce Biopharmaceutical Marketing Manager Europe & India Waters 2011 Waters Corporation

2 Overview Challenges for LC/MS in compliant environments Biopharmaceutical System Solution with UNIFI Software architecture Compliance tools Methods for comparability & consistency 2011 Waters Corporation

3 Characterization ICH Q6B Guidelines Extensive characterization of a biotechnological or biological product is necessary to allow relevant specifications to be established New analytical technology should be utilized when appropriate Characterise primary structure, and higher order structure as possible Define pattern of heterogeneity & demonstrate consistency Product related substances should be characterized Product & process related impurities should be characterised 2011 Waters Corporation Company Confidential 3

4 Biosimilars characterization & comparability EMEA/CHMP/BWP/49348/2005 / / / an extensive comparability exercise will be required to demonstrate that the similar biological medicinal product has a similar profile in terms of quality, safety and efficacy to the reference medicinal product Extensive state-of-the-art the art characterisation studies should be applied to the similar biological and reference medicinal products in parallel at both the active substance and the medicinal product levels to demonstrate with a high level of assurance that the quality of the similar biological medicinal product is comparable to the reference medicinal i product Waters Corporation Company Confidential 4

5 Biotherapeutic Protein LC/MS Applications LCMS intact protein analyses MS exact mass data LCMS peptide p mapping analyses MS and MS E exact mass data Other Common Optical and MS Data workflows SEC UV and SEC-MS analysis IEX UV analysis RP analysis 2011 Waters Corporation

6 Some challenges for analytics in compliant organizations Electronic records EU GMP Annex 11 and FDA CFR 21 Part 11 o Secure data with controls to restrict access o Audit trails o Computers systems validation Validation of analytical procedures ICH Q2 o Accuracy, precision, selectivity, detection limit, quantification i limit, i linearity, i range, robustness as appropriate Analysis times &, especially for biotherapeutics, resolution 2011 Waters Corporation Company Confidential 6

7 Traceability - Linking Information to Records g Sample Sets Standards used for Calibration Original Processing Method Original Instrument Method Unique Analysis Calibration Curves Unchanged Raw Data File E-cord information LC/GC System Used Product Code/ Stage Reagent LIMS ID Who Collected Who Processed Who Reviewed Who Approved 2011 Waters Corporation Company Confidential 7

8 Some challenges for high resolution LC/MS analytics in compliant organizations Secure data storage Most high resolution MS acquisition software runs on workstations only Maintaining traceability Most existing intact protein & peptide map LC/MS workflows involve acquisition, followed by export of data to other software packages to perform specialized data processing and to create reports Some high h resolution MS acquisition iti software and data processing software packages have limited compliance tools for traceability and change control 2011 Waters Corporation Company Confidential 8

9 Workflow for Routine Intact Protein and Peptide Map Analysis by LC/MS Create Acquisition Method and Sample Sequence Data Acquisition Import data into bioinformatics software Prepare Standards & Samples Who did what, when and why? Are my system and data fit for purpose? Reports Compiled Data Management 2011 Waters Corporation Company Confidential 9

10 Overview Challenges for LC/MS in compliant environments Biopharmaceutical System Solution with UNIFI Software architecture Compliance tools Methods for comparability & consistency 2011 Waters Corporation

11 The Waters Biopharmaceutical System Solution An analytical platform for UPLC/UV and UPLC/MS biotherapeutic analysis deployable across unregulated and GxP laboratories XEVO G2 Tof (MS and MS E ) TUV Optical Detector ACQUITY UPLC H-Class BIO BioSeparations Chemistries UNIFI Scientific Information System 2011 Waters Corporation

12 Performance and Usability through Engineered Simplicity Automatically ensuring the system is ready to run 2011 Waters Corporation

13 The Most Extensive Range of Interface Capabilities p Universal source architecture Enables the widest range of ionization techniques to be utilized ESI APCI, ESI, APCI ESCI nanoflow ESI, TRIZAIC APPI, ASAP, APGC p y sources Compatible with third p party (DESI, DART, etc) Simple and tool-free Allowing All i you to t change h between b t ion source options in minutes Waters Corporation Company Confidential 13

14 QuanTof Technology for Stability of Mass Accuracy over Time Measured dmass Accuracy for Peptide THTCPPCPAPELLGGPSVFLFPPKPK in 96 hrs 10 Mass Error (ppm) # of Injections 2011 Waters Corporation Company Confidential 14

15 ACQUITY UPLC H-Class Bio Ultimate chromatographic performance Low dispersion i system sub-2 µm columns Biocompatible system Eliminate system corrosion Best sample recovery Flexibility, robustness Quarternary solvent blending Suitable for RP, IEX, SEC, HILIC Robustness tested for high salt AutoBlend+ for dial-up buffers Needle in flow path design Low carryover performance 2011 Waters Corporation Company Confidential 15

16 Peptide Mapping Reversed-phase chromatography The peptide mapping sample list started on Friday and ran automatically through h the weekend. The data was ready to review upon return to work on Monday. Every third sample is shown, demonstrating excellent reproducibility in both resolution and retention 2011 Waters Corporation Company Confidential 16

17 Transfer Methods With Ease Utilize existing Assets Transfer from UPLC-to-HPLC Future-proof your lab Run HPLC methods on ACQUITY UPLC H- Class 2011 Waters Corporation Company Confidential 17

18 Bioseparation Chemistries BEH Technology Particles Bridged EthylSiloxane/Silica Hybrid EtO 4 Si EtO EtO OEt Tetraethoxysilane (TEOS) EtO EtO + Si 1 EtO CH 2 CH 2 OEt Si OEt OEt Bis(triethoxysilyl)ethane (BTEE) EtO EtO Si Si CH 2 CH 2 Si O O O Si OEt OEt O O Si Si OEt O OEt Polyethoxysilane (BPEOS) O O Et Et n Bridged Ethanes In Silica Matrix U.S. Patent No. 6,686,035 B2 Anal. Chem. 2003, 75, Waters Corporation Company Confidential 18

19 Bioseparation Application Tested Chemistries Protein Separation Technology RP, SEC, IEX Peptide Separation Technology RP Glycan Separation Technology RP, SEC, IEX Oligonucleotide Separation Technology RP 2011 Waters Corporation Company Confidential 19

20 Built on decades of analytical data and informatics experience Waters Corporation

21 KEY FEATURES: Solution Architecture One software for LC with UV and MS detection Robust Set of Data Analysis and Reporting Tools Fully Configurable GxP Compliance Tools Named user login and authentication Electronic signatures Audit trails and Action-Explanation Policies Electronic System Qualification and Maintainance Tools Future-proof: Workstation to Workgroup to Enterprise scalability 2011 Waters Corporation

22 UNIFI Workstation Architecture Workstation Architecture Data/Results Browser Data Processing Database (Data/Results) Instrument Control (ISS) One server handles both functions: Low-level (Database management and Instrument Control) High-level (Data processing and Results browser) Typically a workstation is physically located next to the LC/MS system. Lenovo D20 Workstation Xeon E GHz processor 12 GB GDDR3 RAM Nvidia Quadro FX 1800 graphics card Windows 7 64-bit operating system 2011 Waters Corporation

23 Achieving a Regulatory Compliantready deployment of UNIFI UNIFI capabilities will be extended from the workstation implementation to the compliant-ready architecture now used for networked Chrom Data Systems (e.g. Waters Empower CDS). Data/Results Browser Data/Results Browser Client PC Client PC Company Intranet Laboratory Network Data Server Data Processing Apps Instrument Systems Server Database (Data/Results) Instrument t Control 2011 Waters Corporation

24 UNIFI Scientific Information System Automates routine data processing Task-based, workflow oriented design Intuitive interface tailored to users roles and permissions A method covers acquisition, processing & bioinformatics, reporting, and electronic signatures Powerful SDMS-derived d data mining capabilities 2011 Waters Corporation

25 UNIFI Tools for Compliance Named User Authentication User role(s) Limit capabilities within system/workflows Limit access to data/information Audit trail of user activities ities User action explanation policies (configurable) Electronic Signatures (21CFR11) Who did what, when and why? Are my system and data fit for purpose? Software IQ/OQ System IQ/OQ/PQ (Electronic Documentation) System Maintenance (Electronic Documentation) Data Validation via SHA1 Checksums 2011 Waters Corporation

26 Basic OQ and Extended OQ vs PQ IQ Simple PQ or UAT s OQ IQ Simple OQ Vendor Factory PQ or Testing UAT s PQ or UAT s For many years this was sufficient IQ Extended OQ PQ or UAT s Larger companies through CSV validation groups, Consultants t and GAMP recommendations now increase the PQ to a much higher level and full lifecycle validation needed. IQ Comprehensive Validation Service PQ and full Docs ( VP and VR) Significantly increases the Validation Effort 2011 Waters Corporation Company Confidential 26

27 Instrument Qualification Built-in in Qualification and Maintenance Centre stores: Qualification protocols Engineers certification Qualification reports Qualification results Maintenance log 2011 Waters Corporation Company Confidential 27

28 Methods cover data acquisition to electronic sign-off of a report Systems and Data Acquisition Data Processing and Bioinformatics 2011 Waters Corporation

29 Automated Routine Data Processing 2011 Waters Corporation

30 Automated comparative analysis peptide p map analysis Common and unique peptides identified Coverage maps for reference and analyte Chromatograms for reference (top) & analyte (bottom) 2011 Waters Corporation Company Confidential 30

31 Automated comparative analysis intact protein analysis Protein modifications identified Chromatograms for reference and analyte Deconvoluted annotated mass spectra 2011 Waters Corporation Company Confidential 31

32 Applying a Reporting Template Report Output 2011 Waters Corporation Company Confidential 32

33 Trending of results for larger data sets 2011 Waters Corporation

34 Trending of results for larger data sets Component B Modified Form Trend of intensity: Specific components tracked e.g. a check for modification out of spec, traceable to the batch; or studies of variation in an attribute (glycoforms) Component A Unmodified Form Blanks 2011 Waters Corporation Company Confidential 34

35 Simple Intact Antibody LCMS Analysis Report 2011 Waters Corporation

36 Workflow for Routine Intact Protein and Peptide Map Analysis by LC/MS Create Acquisition Method and Sample Sequence Data Acquisition Import data into bioinformatics software Prepare Standards & Samples Who did what, when and why? Are my system and data fit for purpose? Reports Compiled Data Management 2011 Waters Corporation Company Confidential 36

37 Workflow for Routine Intact Protein and Peptide Map Analysis by LC/MS Create Analysis Method and Sample Sequence Data Acquisition & Processing Reports Compiled, Reviewed & Signed Prepare Standards & Samples Data Management 2011 Waters Corporation Company Confidential 37

38 Relevant literature downloads Search for: Biopharmaceutical System Solution with UNIFI Biopharmaceutical System Solution with UNIFI White Paper UNIFI Scientific Information System Biopharmaceutical System Solution with UNIFI: Intact Protein Characterization Biopharmaceutical System Solution with UNIFI: Simplifying Verification of Peptide Mapping Results Xevo G2 Tof Brochure BioSeparation Products and Columns 2011 Waters Corporation Company Confidential 38

39 Summary Deploying LC with high resolution MS in compliant organizations presents challenges Purpose-built technologies for Biotherapeutic analysis Secure data Traceable results Acquisition, automated data processing, comparative analysis, trending and report generation all within one software 2011 Waters Corporation