Streamlining Regulatory Compliance With a Web-Based Content Management System

Regulated industries have always been challenged to manage the production and flow of documents numbering in the thousands. Today, in addition to complying with Good Manufacturing Practice (GMP), pharmaceutical companies face the pressures of globally distributed teams, increasing regulatory requirements and foreshortened product lifecycles. Far from being transient stressors, these trends will accelerate as countries institute Mutual Recognition Agreements, incenting the parallel launch of new drugs in different countries under a single regulatory submittal process. The ability to streamline drug approvals and related document flows across the enterprise is clearly strategic for the industry.

Content Management Systems (CMS), a standard building block of e-Business sites, can provide many of the features required to manage regulatory compliance. A CMS is a software application that securely stores content components and automatically submits them to a managed workflow. For instance, a CMS would enable a clinical researcher to enter test results on a form, then route the form through review, approval, submittal and archiving steps, keeping an audit trail without the overhead of human administration. A CMS can provide a global repository that enables far-flung researchers to record, collaborate, and reuse research information, while allowing management review and approval of individual submission components.

Benefits of a CMS include:

• Reduced costs of accessing, distributing and archiving documents
• Strong version control improves tracking, ensures stakeholders access correct version of information
• Reduced time-to-market due to accelerated routing and approval
• Elimination of errors caused by multiple parties handling documents manually
• When coupled with a security infrastructure, a CMS can ensure compliance with the FDA's controls for electronic records and electronic signatures (21 CFR Part 11)

This article surveys Web-based CMS solutions, with an emphasis on benefits to the pharmaceutical industry.

Factors

There are many CMS products on the market.  Also, a site could develop its own. What solution is right for you?  How do you make that determination?

In addition to the general technology, quality and support issues surrounding any software investment, there are a number of factors specific to choosing a content management system for use in a pharmaceutical company.  These include:

• Scalability – can it handle millions of documents?
• Workflow features – can it automate your business processes?
• Ability to integrate legacy content
• Ramp-up and quality of professional services support
• Product stability

The complexity of meeting these needs rules out a homegrown approach.  Configuring a CMS to streamline compliance should be approached as a significant capital project requiring dedicated resources from both your organization and the solution provider's.  Basic success drivers of any large IT project apply:  having an executive champion, assembling and getting buy-in from a cross-functional steering committee, properly scoping project phases to manage expectations, and defining ROI criteria for success.  Only with these factors in place can the elements of CMS functionality discussed below translate to business value.

Shouldering the load

The New Drug Approval (NDA) process entails massive document filings, often involving hundreds of thousands of pages originating from around the world.  Whether on paper or in electronic form, the required data includes clinical test procedures, results of animal studies, drug manufacturing and packaging specifications, standard operating procedures and more.  In addition, the value of these "knowledge assets" extends beyond the regulatory process to research, product development, and marketing.  Taken together the aggregate number of pages in a pharmaceutical company's CMS can easily run to several million [1].

Not every web-based CMS product on the market is up to this task.  Many e-Business publishing solutions -- Eprise Participant Server, Interwoven TeamSite and Vignette V/5, for example -- are designed to furnish dynamic, personalized content for commercial web sites, not to handle the document loads associated with industry regulation.  Industrial-strength CMS solutions tend to come from an earlier generation of electronic document management system (EDMS) vendors that have successfully retooled their proven product lines for the Web.  Solutions in this class include:

• Documentum 4i e-Business Platform - extensively deployed as a regulatory compliance solution, Documentum's flagship product enables multiple repositories to be linked together across logical and geographic boundaries to form a single federated content repository for the enterprise.  Scalability is further enhanced by integral caching features and replication services. 

• FileNET Panagon Content Services - FileNET's resume includes document management for large engineering projects, with demonstrated scalability resulting from load balancing, replication services and the ability to extend online storage off-line via optical jukebox.  FileNET also offers Panagon Image Services, a high-volume solution for indexing, storing and manipulating scanned images and faxes. 

• Hummingbird DOCSFusion Server - The DOCSFusion repository occupies the back end of an N-tier architecture built on Microsoft's distributed component object technology (DCOM).  Web application logic resides in a separate tier, promising good scalability as evidenced by the product's large installed base in the document-intensive legal services industry.  DOCSFusion's failover, load balancing and transaction monitoring features also attest to its industrial-strength design.

• Open Text Livelink - Unlike the foregoing products, which originated as client-server EDMS solutions and were later retooled to accommodate Web access, Livelink was designed from the ground up as an Internet collaboration and workflow application.  Livelink can store content in a number of back-end repositories, including Open Text's own terabyte-capable BASIS document collection, relational databases and legacy stores such as Lotus Notes.  Scalability is also supported by flexible N-tier configuration options and caching. 

All of these products can handle the kind of enterprise-wide flow and storage of documents associated with managing compliance.  This is not to say, however, that they are equally effective as compliance automation solutions for the pharmaceutical industry, as we shall see below. 

Automating compliance

There are consensus standards for most products and services traded worldwide, as well as standards for quality management systems, such as the International Standardization Organization (ISO), U.S. Food and Drug Administration (FDA) and Institute of Electrical and Electronics Engineers (IEEE).  Three of the vendors mentioned above, Documentum, FileNET and Open Text, specifically target standards compliance as a key value-add for their products.  (This is not to suggest that Hummingbird's content management solutions are unsuitable for this purpose, only that the vendor has traditionally served other markets.  In particular DOCSFusion is a dominant records management solution in the legal services industry.) 

For example, an Open Text case study cites Livelink as "critical in helping [Canadian telephone giant] Nortel achieve ISO 9001 accreditation."  In 1998 the group using Livelink successfully demonstrated the "quality of documentation and thoroughness of process control" required to receive certification.  Similarly, Documentum and FileNET cite successes in ISO 9000 compliance, management of standard operating procedures and other regulated processes in diverse manufacturing industries including pharma. 

Industry-specific regulatory mandates drive each company's functional requirements for document management and process automation.  Pharmaceutical firms, for example, face the NDA process, GMP and, with regard to electronic documents, FDA 21 CFR Part 11. 

Documentum has an especially impressive record in supporting these requirements.  In a CMS deployment at Bayer Corporation, for example, Documentum automated the workflow that defines how standard operating procedure (SOP) documents are routed for approvals.  An electronic signature capture application lets Bayer record 21 CFR Part 11 approvals online.  Once all signatures are obtained and the effective date is entered, the document is moved to a secure repository where SOPs reside.  Bayer credits the system with providing a document management foundation for Quality Assurance, Regulatory Affairs, Validation, and Engineering.  French pharmaceutical firm Sanofi and Boots Healthcare International (BHI) have similarly deployed Documentum to streamline their regulatory approval processes. 

In keeping with its focus on web-enabled collaboration, Open Text touts Livelink as a platform for improving communication between researchers and managing knowledge assets. These features are particularly valuable during the drug discovery process.  At Glaxo Wellcome, for instance, Livelink is being used to create "a collaborative workgroup area on the Web where … geographically dispersed teams work together on projects, develop common goals and take advantage of discussion areas," according to Joe Felix, Director of Commercial Information Technology. 

Both Open Text and FileNET cite the ability to streamline compliance as a key benefit of their products in the pharmaceutical industry, though neither offers relevant case studies in its collateral.  FileNET in particular omits the industry from its list of targeted verticals. 

Accommodating the past

The 12 to 15-year product life cycle for new drugs ensures that many forms and documents, both historical and going forward, will exist in non-electronic "legacy" formats.  Putting these records under content management is frequently the single largest cost-driver in industrial CMS deployments.  Both the product's ability to incorporate legacy data and the vendor's tool and service offerings determine how smoothly conversion will go. 

Documentum 4i, FileNET Panagon and Open Text Livelink can accommodate electronic documents in a variety of formats, including most versions of Microsoft Word and Excel, text, and Lotus Notes.  Documentum also supports optional integration with Notes Mail.  All of these products can access relational data stored in SQL Server or Oracle tables as well. 

Paper documents and microfiche must be scanned, but this task, though laborious, can usually be accomplished by relatively unskilled, low-cost resources.  A more significant cost driver is categorizing converted documents by adding appropriate metadata.  This requires enough analysis and understanding of each document to meaningfully classify it.  Putting documents online without the intelligence bestowed by metadata is putting light under a barrel; such documents are effectively unmanageable. 

Document conversion is a specialized niche that should be planned and executed as a subproject of your overall CMS deployment.  The vendors discussed in this paper offer varying degrees of tool support for the process.  For instance, FileNET's Panagon Capture Professional facilitates the import and indexing of a variety of unstructured record formats including scanned paper, faxes, email, Electronic Document Interchange (EDI), and HTML and XML documents.  The company also offers Panagon Image Services, a companion product to its Content Services offering, for applications requiring high-throughput indexing and storage of scanned images and faxes. 

By contrast, Documentum and Open Text emphasize structured data and offer tools and services for modeling document content as XML.  These vendors support imaging and unstructured data conversion through integration partners. 

Ramp-up and quality of professional services support

Have no illusions:  no off-the-shelf product, whether web-based CMS or classical Electronic Document Management System (EDMS), is going to solve your compliance needs without extensive customization.  In all likelihood significant changes to your organization's business processes and concomitant training will be required as well, since systems are only as good as the people who use them.  Facing these realities and accounting for them in your project plan will go a long way towards mitigating cultural risks. 

Given that CMS customization will be required, the question to ask of potential vendors is how easily their products can be configured to your company's needs.  An important corollary is how strongly the vendor's professional services arm or partner can support customization. 

Perhaps the most aggressive solution for automating the NDA process is GMPharma, a joint offering of Documentum and PricewaterhouseCoopers.  The co-branded product and services offering aims at the heart of the CMS implementation barrier:  the tailoring of powerful generic features through pre-configured templates, work-flows and lifecycles to meet the myriad complex requirements of GMP.  GMPharma purports to be "an out-of-the-box solution for managing GMP documents that meets or exceeds requirements for compliance with FDA 21 CFR Part 11, EC GMP Vol. 3&4 Annex 11, ISO 9001, WHO [World Health Organization] GMPs, and other international standards."

The wide ranging costs of GMPharma deployments – from $750,000 to $20M – indicate how significantly the installation can vary from company to company. 

Open Text's vertical solution for the pharmaceutical industry, PharMatrix, is foremost a Project Life Cycle Management tool targeted at the early, pre-clinical phases of new drug development.  According to the vendor,  "the powerful document management and collaborative capabilities of PharMatrix also make it very suitable (and indeed it is being used) for clinical trial and manufacturing support."  This does not, however, imply out-of-the-box configurability for NDA compliance automation. 

Open Text customers in the pharmaceutical industry include Abbott Laboratories, Amgen, Chiron Corporation, F. Hoffmann La-Roche AG, Glaxo Wellcome, Worldwide Clinical Trials Inc., Pfizer Inc., U.S. Pharmacopia Convention, and Zimmer. 

Rather than offering an off-the-shelf configuration for pharmaceutical companies, FileNET maintains relationships with several "strategic implementation partners," including Trinity Technologies, Druid, KPMG, and Crowe Chize.  FileNET customers in the industry include Bayer, Glaxo Wellcome, Merck, Smithkline Beechem, Warner Lambert, and Abbott Labs, among others. 

Live long and prosper

It takes over a decade to research, develop, approve and market a new drug.  In terms of information technology this is a very long time, on the order of 10 doublings -- a 1000-fold increase -- in processor power, according to the rule of thumb known as Moore's Law.  The advent in the last five years of Web-based commerce that takes place in "Internet Time" suggests that business processes will evolve almost as rapidly.  The upshot is that the functional requirements, business logic and user profiles underlying your CMS investment are guaranteed to change even as the ink dries on the purchase order. 

Taking account of this knowledge in the selection process can help mitigate the risk of obsolescence.  While no technology is future-proof, certain design features can improve the odds that your CMS will be capable of adapting to change rather than succumbing to it.  Systems that adhere to industry standards, have flexible configuration options and can readily be integrated with external applications stand the best chance of living long, productive lives.  Also assess each vendor's prospects for longevity by investigating the vendor's background and financial situation. 

Standards.  Adherence to standards is one of the things that makes Web-based applications attractive in the first place. All the products discussed in this paper offer browser-based user and administration interfaces, ensuring standardization of the presentation layer on HTML and HTTP/HTTPS, vendor-neutral, de jure technology standards.  (Documentum 4i and FileNET Panagon offer alternative, client-server-style interfaces as well.)  Make sure the browser versions supported match your enterprise standards.  Other standards to look for include: 

• LDAP (Lightweight Directory Access Protocol) - enables systems to leverage existing user directories to expedite account, security and profile setups
• SMTP (Simple Mail Transport Protocol) - the standard for Internet mail, enjoying broader industry support than proprietary e-mail transports such as Microsoft MAPI
• ODMA (Open Document Management API) - an open standard for document management interoperability, now part of an open source initiative called DMware
• WebDAV (Web Distributed Authoring and Versioning) - extends the Web's core network protocol, HTTP, with collaborative authoring features
• Adobe PDF (Portable Document Format) - the de facto standard for high-fidelity image rendering
• XML (Extensible Markup Language) - an open standard for platform-neutral data exchange

XML deserves special mention in the context of content management.  XML separates the content of a document from its presentation, allowing content components to be re-purposed across different e-Business applications and delivered through multiple media such as the Web, wireless devices, PDF, print, and CD.  XML also acts as lingua franca for migrating data between systems, including both the import of data from and export of data to structured sources (e.g., RDBMS, other applications).  XML can support globalization through the use of double-byte Unicode.  Finally, XML documents can be validated against layout and semantic specifications (DTDs or Schemas), ensuring conformance to regulatory submission requirements. 

Flexible Configuration.  A vendor's flexibility in supporting different system configurations can be important, especially if network bandwidth and reliability vary between offices.  Features such as replication, remote caching and flexible partitioning of server tiers can help tailor a CMS to your infrastructure, both now and in the future. 

Integration.  While streamlining regulatory compliance may be the primary goal of your CMS deployment, planning to leverage content management across multiple business functions can bolster return on investment.  All of the products mentioned in this paper offer pre-configured interfaces to major third-party systems. 

Documentum's integration support is the broadest, providing out-of-the-box "eConnectors" to ERP systems (SAP and PeopleSoft), CRM systems (Siebel), office applications (Microsoft Office and any ODMA-compliant application), XML tools (ArborText’s Willow and SoftQuad’s XMetaL), and application/commerce servers (ATG, BEA, Broadvision, IBM, Sun, and others) for building custom e-Business applications.  Open Text offers add-ons called Livelink modules for connecting to SAP R/3, CORBA systems, LDAP or NT Domain directory services, Lotus Notes and e-mail systems.  In addition, most CMS products provide full-featured Application Programming Interfaces (APIs) for custom integrations. 

Conclusion

Web-based content management systems hold great promise for streamlining regulatory compliance in the pharmaceutical industry.  The best solution candidates come from established EDMS vendors proactively evolving their product lines towards open standards and e-Business features.  Four such vendors are Documentum, FileNET, Hummingbird and Open Text. 

The suitability of these vendors' products to the compliance needs of the pharmaceutical industry has been explored, with the conclusion that Documentum's GMPharma offering (developed jointly with PricewaterhouseCoopers) is the most complete.  Moreover, only Documentum cites specific deployments of drug company compliance applications in its literature.  Hummingbird targets primarily the legal and financial services industries.  Open Text Livelink and its vertical offering PharMatrix emphasize collaborative applications most relevant to drug discovery (as opposed to approval), while FileNET Panagon has the strongest support for bringing images and other unstructured formats under records management.