Upload
others
View
2
Download
0
Embed Size (px)
Citation preview
accelrys.com
TECHNOLOGY BRIEF
1
THE CHANGING ROLE OF INFORMATICS IN THE LAB-TO-PLANT LIFECYCLE
Many leading life sciences companies have introduced cost-reduction initiatives to automate
routine, non-value-added tasks related to data capture, cataloguing and documentation activities as
products move from discovery through development to late-stage quality control, manufacturing and
commercial operations. In most regulated companies, the key documentation needs in discovery and
early development tend to be related to intellectual property (IP) protection, while approximately 70%
of laboratory resources from later development through commercialization are focused on meeting
compliance requirements.
Within the lab-to-commercialization process, the drive to “go paperless” is a strategic initiative that
offers demonstrable operational benefits in improving productivity, reducing cycle times and enabling
organizations to leverage experimental and operational data generated along the entire research-
development-manufacturing continuum. For example, quality and pilot plant data generated during
late-stage commercialization can accelerate early product, process and analytical method development
by enabling better Quality by Design (QbD) experiments that are based on real-world conditions,
experience and insight. Likewise, the proper management and exchange of process and product
design, execution and documentation creates enterprise-wide intelligence that accelerates product
commercialization cycle times.
GOING PAPERLESS FROM LAB TO PLANT
Capturing and harmonizing data in product R&D and manufacturing/quality facilities to improve
Operational Excellence
TECHNOLOGY BRIEF: GOING PAPERLESS FROM LAB TO PLANT
2accelrys.com
An electronic environment drives improved “Scientific Innovation Lifecycle Management”by enabling
the automation of critical processes and data harmonization across research, development and
manufacturing/quality environments. This functional capability is facilitated by the Accelrys Enterprise
Platform, a scientifically aware informatics platform that integrates critical lab-enabling software
functionality with existing enterprise systems and information sources and enables organizations to
deploy scientific software and services solutions along the end-to-end, lab-to-plant lifecycle—speeding
“science to compliance” for organizations that rely on scientific innovation to differentiate themselves.
This technology brief reviews recent initiatives by science-based organizations to develop and deploy
software that spans the lab-to-commercialization lifecycle using data standardization/harmonization
technology and electronic lab notebooks (ELNs) to streamline technology transfer. The brief also
addresses the usefulness of a single, unified, scientifically aware platform in accomplishing technology
handoffs along the lab-to-plant continuum, as well as the importance of consistent, standard procedures
for data and process management across the end-to-end innovation lifecycle.
INDUSTRY CHALLENGES TODAY
Today’s pharmaceutical, biotech and generic businesses are challenged to improve product quality,
productivity, return on investments and compliance, while at the same time producing double-digit
growth for stakeholders. These challenges will be compounded over the next few years as major
marketed pharmaceuticals lose patent protection and companies struggle with anemic product
pipelines and externalization strategies. Globalization in emerging markets and new competitive forces
are capturing the attention of senior management concerned with revenue growth and long-term
management of financial resources. As a result, organizations are reevaluating the entire “product/
portfolio lifecycle” from research through development to manufacturing, especially with a view to
advancing information technology (IT) systems to address evolving business ecosystems.
One significant challenge is the large amount of data currently being generated across enterprises in
support of R&D and Quality Assurance/Quality Control (QA/QC) activities in commercial plant operations.
This data explosion is a valuable asset that can positively impact both enterprise operations and the
future development and scale-up of new therapeutics. Unfortunately, much of this data is contained in
paper systems that are difficult to access or in “silo-based” electronic systems that are difficult to utilize
and optimize. Increased externalization often results in even more paper, negatively impacting the
success and value of collaborations.
TECHNOLOGY BRIEF: GOING PAPERLESS FROM LAB TO PLANT
3accelrys.com
As a new product emerges from R&D into commercial operations, FDA guidelines on electronic
records and electronic signatures (Title 21 CFR Part 11) and QbD, including recommendations of the
International Conference on Harmonization (ICH), place additional demands on organizations in the
highly regulated pharmaceutical and biotechnology industries. These regulatory demands provide a
compelling rationale and framework for improved quality systems and electronic records. Key to the new
strategy is a risk-based approach as defined by impacts on human health. While most discovery and
R&D areas are low risk, the QA/QC functions—at both the clinical materials and product release stages
within the production and pilot arena—clearly fall into a “high risk” definition.
FROM SCIENTIFIC INNOVATION LIFECYCLE MANAGEMENT TO PROCESS MANAGEMENT AND COMPLIANCE
As a result of these challenges, over the last five years the drug development industry has been seeking a
unified scientific informatics platform to enable and optimize the management of both R&D information
and manufacturing QA/QC/batch record data. Until today, this has been a daunting challenge. Many
companies have cobbled together disparate IT systems in an attempt to meet these demands; however,
at best, the result has been an interminable custom-coding process with serious total cost of ownership
and validation/compliance shortcomings. This is unfortunate because, when done right, a unified
platform approach to scientific informatics should significantly advance both Quality by Design (QbD)
and Operational Excellence initiatives across global business networks.
In January 2012, Accelrys announced the acquisition of VelQuest Corporation. Both companies
supported the life sciences industry with Accelrys focusing on upstream Discovery and R&D while
VelQuest focused on downstream QA/QC in Development and Manufacturing. The merger has resulted
in the development of a unique electronic environment for scientific process management and
compliance spanning discovery/research/development and quality/production facilities. The integration
of Accelrys and VelQuest technologies, made possible by the Accelrys Enterprise Platform, is now a key
enabler of Scientific Innovation Lifecycle Management strategies aimed at enabling organizations to
capture, manage and share product and process R&D information including Chemistry, Manufacturing
and Control (CMC), bioanalytical and formulations data; bioprocess and process chemistry; pilot
operations information; and commercial production QA/QC data in an all-electronic environment.
The genesis of this platform was originally outlined in an Accelrys program involving Bristol-Myers
Squibb, AstraZeneca, Johnson & Johnson and VelQuest Corporation. In 2010, these companies met
with Accelrys to investigate development of an informatics infrastructure/platform that would allow
movement of R&D analytical methods and manufacturing process data across boundaries.
TECHNOLOGY BRIEF: GOING PAPERLESS FROM LAB TO PLANT
4accelrys.com
The charter was as follows:
This project is to define a standard way to represent any analytical method and method schema.
This schema is intended to be independent of any particular software, hardware or type of method.
This enables the movement of methods between tools, vendors, organizations and geographies. This
standard must be specific and robust enough that a wide variety of methods can be represented and
when transferred, little or no detail and clarity will be lost. Fundamental to achieving this is the ability
to express a decomposition of laboratory operations (lab unit operations, parameters) with sufficient
detail. In addition, the sequence of operations, dependencies and optional branch points must be
captured as well.
The partnering organizations determined that the charter objectives could be met with an interchange
based as closely as possible on international industry standards ANSI/ISA-88 (covering batch process
control) and ANSI/ISA-95 (covering automated interfaces between enterprise and control systems),
both of which are commonly used in Manufacturing. The result of this initiative is the Accelrys Process
Management and Compliance Suite that leverages the Accelrys Enterprise Platform in support of
Scientific Innovation Lifecycle Management.
THE PAPERLESS LAB – ELNS IN R&D AND QA/QC
Automation initiatives in pharma/biotech production over the last few decades have been driven by the
need for precise control of production processes and cost savings. Typical Supervisory Control and Data
Acquisition (SCADA) and Manufacturing Execution System (MES) implementations are good examples
of such automation. Today the production environment is under further scrutiny for opportunities to
cut costs in other closely related, non-value-added functional areas including the large number of paper
processes still used during the development and early manufacturing stages of a new product. These
“e-lab” initiatives have received attention as one of a small number of critical-path issues that, if solved,
will yield significant operational and cost savings.
As scientific documentation moves from research through development to commercialization, the
fundamental informatics requirements change dramatically, evolving from a free-form, open structure
for initial ideation through a more structured (but flexible) experimental set for optimization to a rigid
SOP-based method execution platform for quality control in manufacturing. In this lifecycle, there is a
need to rapidly acquire and share scientific insights across the continuum from lab to manufacturing.
Before Accelrys and VelQuest joined forces to deliver the Accelrys Process Management and Compliance
Suite, transferring product and process information from early development through commercialization
was a significant challenge (Figure 1).
TECHNOLOGY BRIEF: GOING PAPERLESS FROM LAB TO PLANT
5accelrys.com
Since they first appeared in the late 1990s, ELNs have predominantly been utilized to document
experiments and capture intellectual property for patent defense purposes. In fact, many of the
early research ELNs were simply secure word processing and spreadsheet software products. Today’s
multidisciplinary research ELNs have evolved significantly to the point where they now offer specific
functionality supporting synthetic, analytical, (bio)formulations and (bio)process scientists as well as
biologists working in areas from screening to preclinical and clinical development.
As analytical methods progress through the drug development process, the degree of “blue sky”
flexibility versus “locked-down” execution will vary for different scientists depending on where they are
along the lab-to-plant continuum; however, the final validated QC test and Certificate of Analysis for
both the product and the process in commercial operations is always the all-important outcome. By
using a flexible analytical development notebook during the R&D phases of this process (such as the
Accelrys Electronic Lab Notebook) coupled with a QC notebook at the commercialization phase (such as
the Accelrys Lab Execution System), organizations gain a unified, end-to-end process management and
compliance environment from development through manufacturing (Figure 2).
Figure 1: Key documentation and technology handoffs from Research through Optimization to Production with critical technology transfer into quality control
TECHNOLOGY BRIEF: GOING PAPERLESS FROM LAB TO PLANT
6accelrys.com
An ELN used in an R&D environment requires an open structure for handling general observations and
experimental detail. This includes the flexibility to adjust scale, re-order process steps, substitute reagent
components or change concentrations when developing analytical test method processes. The research
notebook enables scientists to capture both the processes they perform and the interpretation of
experimental results.
In a regulated QA/QC environment, however, an open structure is not preferred and, in fact, is a
compliance liability. A QA/QC ELN must be capable of handling highly structured, method-centric
operational protocols with all lab systems (instruments, SOPs, reagents, etc.) integrated into the
e-method, as well as large volumes of samples and associated information. Rigorous attention to
compliance is essential for the QA/QC ELN. For example, reagents, instruments and devices used in the
execution of test methods must be automatically verified for their “compliance state” prior to use, and
QA/QC data must be validated in real-time. The major differences between research ELNs and QA/QC
ELNs are outlined below (Figure 3).
Figure 2: Progression of a method from development to commercial QC operations and key functional requirements used in coupling the Accelrys Electronic Lab Notebook to the Accelrys Lab Execution System
TECHNOLOGY BRIEF: GOING PAPERLESS FROM LAB TO PLANT
7accelrys.com
Transferring methods between the development and QA/QC areas is typically an enormous burden
for organizations, often requiring them to relocate the method development and process team to the
pilot or production site for extended periods to ensure complete and accurate technology transfer.
Integration between the Accelrys Electronic Lab Notebook and the Accelrys Lab Execution System
addresses this transfer process by enabling an interchange of method information between our ELN
technologies using the ISA S88/S95 standard for process definitions. This method exchange capability
reduces the time to re-implement a method within the QA/QC infrastructure and enables better
development and tracking of methods.
LEVERAGING DATA ASSETS – THE DATA VALUE CHAIN
Both research and QA/QC ELNs need to utilize lab data effectively so that scientists can extract full value
from it. This applies to operational reporting and release processes as well as data mining, trending and
feedback into Quality by Design initiatives. As shown in Figure 4, the Accelrys systems supporting these
functions are the Accelrys Lab Execution System and Accelrys Electronic Lab Notebook for capturing
data (with the Accelrys Instrument Data Service streaming instrument data) and the Accelrys Enterprise
Platform for aggregating, processing and reporting information.
RESEARCH ELNS QA/QC ELNSFocus Experiment-based Method and procedure-based
Primary User Scientist Analyst/Chemist/Operator
Business Drivers Intellectual property & knowledge
sharing
Compliance & lab operations
productivity
Design Approach Research & project-centric,
specialized scientific functionality
Highly structured; method-centric,
preparation-centric, compliance-
centric
Search Approach Project and experiment-based,
results data mining, personnel,
molecule/therapeutic
Sample, manufacturing lot,
equipment, personnel
Data Capture Drivers
Research instruments, image
analysis, result summaries and
aggregation, dates, materials
Data for preparations, calculations,
and instrument compliance-state
checks; raw instrument data capture
for review and trending purposes
Figure 3: Research ELNs vs. QA/QC ELNs – Open vs. structured approaches
TECHNOLOGY BRIEF: GOING PAPERLESS FROM LAB TO PLANT
8accelrys.com
The Accelrys Enterprise Platform streamlines data access and reporting across the enterprise by
providing a common “view” of underlying data and a standard process for extracting, transforming and
loading data using a single common data structure and format. Querying and reporting components
can be exposed as web services, enabling multiple applications or internal configured interfaces to
access and display information in a manner most appropriate for various corporate “stakeholders.”
Business rules and quality checks can be built into these re-usable components to ensure that data
complies with necessary standards as it moves through the organization. A single platform supports
flexible data mining and query activities in upstream R&D, as well as the compilation of more structured
therapeutic dossiers required for downstream regulatory submissions.
EXTENDING THE DEVELOPMENT ELN INTO LAB EXECUTION QA/QC
The Accelrys Lab Execution System has been deployed and proven in numerous global pharmaceutical,
biotech and CRO/CMO organizations. Key benefits as presented at Accelrys’ annual International
Meeting on Automated Compliance Systems (IMACS) include more than 20 percent productivity/
cost improvements, 50-75 percent cycle-time reduction in quality operations and significant overall
compliance risk reduction. The Accelrys Electronic Lab Notebook has been deployed in many of the
same organizations to support formulations, process (CMC) and analytical development groups.
Figure 4: The Accelrys Enterprise Platform facilitates direct data capture from all instruments (via Accelrys Instrument Data Service)while also providing a data querying/analytics platform supporting product and process design and decisions in development and QA/QC operations.
TECHNOLOGY BRIEF: GOING PAPERLESS FROM LAB TO PLANT
9accelrys.com
Over the last few years these companies have been requesting a “Product/Process Development
electronic environment” for use in executing and documenting experiments and sample processing
during the development stages of new entities. During the Product/Process Development phase, the
therapeutic entity is known and research is focused on deriving the optimal formulation, manufacturing
process conditions, testing and production environment to achieve the highest purity with the optimal
yield at the lowest cost. New analytical test methods are being developed which require optimization
and validation experiments to transfer robust procedures to QA/QC operations. Across this continuum,
scientists require an electronic environment for process management and compliance that supports
both flexible “authoring”and structured “execution.” These capabilities are made possible now with the
Accelrys Process Management and Compliance Suite (Figure 5).
This technology combines flexible development with rigid execution. In the end when the product and
technology are transferred to commercial operations, the validated QC analytical test method is already
in a validated Accelrys Lab Execution System, executable for routine QA/QC use in the lab.
Figure 5: A collaborative technology landscape. Through XML-based transfer, process parameters are passed from the Accelrys Electronic Lab Notebook to the former VelQuest ELN (now Accelrys Lab Execution System) for procedure execution with results then centrally stored and accessible using the Accelrys Enterprise Platform.
TECHNOLOGY BRIEF: GOING PAPERLESS FROM LAB TO PLANT
10accelrys.com
ACCELERATING SCIENTIFIC INNOVATION LIFECYCLE MANAGEMENT WITH IMPROVED PROCESS MANAGEMENT AND COMPLIANCE
With 9 of the world’s top 10 pharmas already using the Accelrys Electronic Lab Notebook and Accelrys
Lab Execution System for analytical method development, validation and sample analysis, the Accelrys
Process Management and Compliance Suite offers analytical, development and QA/QC labs a unique
opportunity to remove paper processes while supporting end-to-end, lab-to-plant analytical and
process workflows (Figure 7).
The Accelrys Process Management and Compliance Suite includes an Instrument Data Service (IDS)
comprising a comprehensive selection of out-of-the-box, validated instrument connections.
These instrument connections ensure the rapid, efficient and cost-effective replacement of paper
processes in a fully automated and electronic lab environment, free of transcription errors, where
all sample information is centralized for rapid reporting, data investigations and capacity resource
management (Figure 8).
Figure 7: The Accelrys Process Management and Compliance Suite supports the early and agile development, optimization and validation of analytical methods; high-throughput, compliant execution of sample analysis in regulated and non-regulated labs; and automated, locked-down procedure execution via electronic batch records during late-stage quality control and manufacturing in GMP environments. Common standards between systems ensure rapid transfer of procedures to production and new opportunities for data mining, analytics and visualization.
TECHNOLOGY BRIEF: GOING PAPERLESS FROM LAB TO PLANT
11accelrys.com
Accelrys’ unique use of S88 and S95 ISA standards to manage methods and procedures across the entire
method development to sample analysis continuum enables the accurate, uniform storage of enterprise
data in a single centralized database. Uniform data accelerates data mining, reporting and sharing for
continuous insight and process improvement (Figure 9).
OPERATIONAL BENEFITS OF IMPROVED PROCESS MANAGEMENT AND COMPLIANCE
The Accelrys Process Management and Compliance Suite is “purpose-built” to assist scientists in
designing, executing and managing critical lab and plant compliance tasks from upstream R&D to
downstream QA/QC operations. The management applications can be deployed as independent
Web-based solutions or integrated with the Accelrys Electronic Lab Notebook, Lab Execution System or
Electronic Batch Records applications. Minimal software configuration means total cost of installation
Figure 8: Empower2, Chromeleon and ChemStation: Three of many instrument interfaces supported by the Accelrys Instrument Data Service to automate instrument data capture, processing and storage. The IDS includes direct raw data capture from the RS-232 port, file parsing from a file store or direct communication with the scientist’s desktop software via a chromatography data system.
TECHNOLOGY BRIEF: GOING PAPERLESS FROM LAB TO PLANT
12accelrys.com
and ownership is low. Because the applications are built for quality operations (including validation
documentation), the system can be deployed and made operational in a few months compared with
the protracted implementation of traditional LIMS technology. The Accelrys Process Management
and Compliance Suite can also be integrated with existing commercial LIMS installations where
specific application capabilities have not been programmed and customized by a LIMS vendor or
implementation consultant.
Developed in conjunction with several global pharmaceutical companies and utilizing proven procedure
execution and workflow management technologies, the Accelrys Process Management and Compliance
Suite provides a range of applications to support the Accelrys Lab Execution System, Accelrys Electronic
Lab Notebook and Accelrys Electronic Batch Records environments including capabilities for managing:
• Environmental monitoring
• Inventories
• Samples and specifications
• Instrument metrology/calibration and maintenance
• Stability studies
Figure 9: A centralized data warehouse utilizes the S88 and S95 industry standards to represent analytical methods, recipes and equipment. Uniform data streamlines the capture and exchange of analytical methods and sample analysis across the organization (slide presented by Johnson and Johnson at IMACS 2012).
TECHNOLOGY BRIEF: GOING PAPERLESS FROM LAB TO PLANT
13accelrys.com
A set of standard technology modules enables IT/IS and System Administrators to implement any of
the above applications without the need for vendor or third-party resources, significantly accelerating
installation/validation while also reducing or eliminating traditional LIMS customization/configuration
issues. The system is designed to track and trace materials, samples, instruments, specifications, reports
and data transfers in enterprise cGLP- and cGMP-compliant environments.
With all data centrally and consistently captured, analytical groups can quickly find sample information,
compare and contrast information across multiple samples and investigate sample genealogies (Figure 10). Dashboards based on sample specification parameters and business rules instantly reveal any
deviations from specification. Not only do scientists spend less time reviewing sample results, but
analysts can respond more rapidly when deviations occur (Figure 11).
Figure 10: Different customer-created views of data captured in analytical systems. These examples show how analysts can quickly find and report single sample results, as well as accessing, comparing, contrasting and visualizing information for multiple samples.
TECHNOLOGY BRIEF: GOING PAPERLESS FROM LAB TO PLANT
14accelrys.com
EXTRACTING PROCESS UNDERSTANDING AND REAL-TIME CONTROL WITH ADVANCED ANALYTICS AND REPORTING
By electronically capturing and accessing consistent data from early design and optimization
experiments through full commercialization, management can gain improved insight into process
and product quality. By using the Accelrys Enterprise Platform with the Pipeline Pilot scientific
authoring application, scientists can easily configure reports, trending reports and operational
dashboards providing real-time updates on development program progress and commercial Quality
by Design process improvements and/or control. Using defined protocols, Pipeline Pilot can reach
into development and execution databases to tee up the needed data for advanced knowledge
management and decision making (Figure 12).
Accelrys’ IMACS (International Meeting on Automated Compliance Systems) conference provides a
podium for customers to present their successes using Accelrys Process Management and Compliance
applications and the Accelrys Enterprise Platform. Customers have reported:
• Up to 25 percent productivity improvement
• 50 percent reduction in cycle time
• 10-fold reduction in compliance risk
At the 2012 IMACS conference in Boston, Bristol-Meyers Squibb (BMS) presented their projected
operational benefits from deploying Accelrys Enterprise Platform technology (Figure 13).
Figure 11: A dashboard for a specific set of analytical procedures in the QC lab. Color coding shows the progress of sample processing with any deviations flagged for review. Clicking on the colored flag drills down to specific audit detail and source data files.
TECHNOLOGY BRIEF: GOING PAPERLESS FROM LAB TO PLANT
15accelrys.com
Figure 13: Benefits gained by Bristol-Meyers Squibb as a result of deploying Accelrys technology in analytical labs. BMS scientists were able to accelerate technology transfer from method development to regulatory reporting, saving six weeks in the process.
Figure 12: Having captured the product and process details across the lab-to-plant continuum, organizations can leverage the data to gain new insights into capacity management, quality and operational efficiencies that yield improved product quality, more compliant operations and lower costs of goods sold.
TECHNOLOGY BRIEF: GOING PAPERLESS FROM LAB TO PLANT
16accelrys.com
CLOSING THE GAP BETWEEN INNOVATION AND COMMERCIALIZATION
Faced with revenue erosion resulting from expiring patents and questionable new product pipelines,
pharma is sharpening its pencil to improve operational cost controls. For decades, most data has been
paper-based, requiring numerous non-value-added checks to ensure end-to-end data integrity and
quality from product development through product commercialization. These paper-based systems are
becoming even more problematic as life sciences companies increasingly externalize operations.
Today’s technology can eliminate these paper systems and replace them with efficient electronic
environments supporting science to compliance. Within any pharmaceutical company there are three
key informatics/ELN design issues depending on where scientists are working within the lab-to-plant
continuum. Research scientists require an open-ended, free-form ELN for experimental design, results
capture and IP protection. QA/QC scientists in cGMP environments need just the opposite—a highly
structured, procedure and method-centric operation with full instrument integration and data exchange
capabilities with other IT systems (LIMS, ERP, MES, etc.). Between discovery R&D and manufacturing QA/
QC are the unique needs of the development groups. Here, flexible experiment design coupled with
parameter variations are the key informatics documentation needs. This development informatics/
ELN environment enables quick technology transfer of ruggedized, automated test methods to quality
operations as well as process parameters to pilot plants and manufacturing facilities. When the molecule
goes into full commercial production, the informatics/ELN platform enables recursive data access
supporting QbD efforts and continuous product/process improvements.
Companies can adopt an informatics approach that effectively connects the innovation and
commercialization cycles with high fidelity data that retains contextual information as a project
moves through R&D into manufacturing. Scientific Innovation Lifecycle Management supports
this approach, and the Accelrys Enterprise Platform provides a comprehensive, scientifically aware
informatics framework for capturing and harmonizing data along the product R&D and manufacturing/
quality continuum.
TECHNOLOGY BRIEF: GOING PAPERLESS FROM LAB TO PLANT
17accelrys.com © 2011 Accelrys Software Inc. All brands or product names may be trademarks of their respective holders.
WP-0503-1012
Combining best-in-breed ELNs, instrument integration and LIMS functionality with an interchange based
on international industry standard XML definitions ISA-88 (batch process control) and ISA-95 (automated
interfaces) bridges the innovation productivity gap between development and commercialization,
enabling successful, end-to-end technology transfer across new product development and production
QA/QC operations. Organizations adopting this proven informatics IT solution will experience:
• Better decisions through optimized experimentation and sample processing with real-time results
• Enhanced productivity through better understanding of the design space critical to
Quality by Design
• Faster time to market through shorter cycle times and reduced latencies between cycles
• Improved compliance through automated execution and reporting
• Effective externalization through enhanced collaboration within globalized R&D and across
dispersed teams
To learn more about the Accelrys Process Management and Compliance Suite, go to
accelrys.com/pmc