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