With the onset of electronic submissions to the Food and Drug Administration and the need for paperless workflows to meet management goals of increased efficiency, many new information technology systems are being implemented at Bayer Pharmaceutical. This case will focus on the legacy system and the benefits the proposed electronic system will bring.
In the past, the compilation of NDAs was a difficult and complex undertaking. Copiers needed to be constantly maintained and even a truck rented to deliver the volumes of paper to the FDA. While it is still a complex process, the Regulatory Affairs department of Bayer Pharmaceutical handles all FDA contact for submitted drugs. Liaisons are designated for each drug and have complete access to reviewers. They are responsible for handling all review requests and maintaining FDA regulations for each of their assigned drugs. It is also Regulatory Affairs' responsibility to submit all documents to the FDA, including NDAs. This is done through hard copies that trickle down to the corresponding people in charge of each drug. For example, an investigator in the field must be approved by an Investigational Review Board in order to start administering a proposed drug to human patients. This is usually done in the latter phase of the testing procedure. Once the review board approves the investigator for the protocol in which they wish to take part, the paper work is sent to various departments for signatures by assigned directors. The paper copy is then sent to the liaison in Regulatory Affairs who must then make sure all procedures have been followed to comply with regulations. The liaison submits the proper copy to the FDA while another copy is archived. The document is given an archival number, scanned into the electronic archival database as an image, and filed with millions of other documents. Every department that sees this document, however, keeps a copy. Many of these copies are stored in different and unrelated systems. The archival system in Regulatory Affairs is a legacy database that was developed almost a decade ago and stores millions of links to hard copies archived in the files. The medical groups (departments) store their copy of this document in a newer relational database. This system assigns numbers to the document in a similar way to the Regulatory Affairs' database, but works much better for electronic distribution. The problem with the database is that if changes need to be made, the current document becomes useless. It must be printed for any revisions and version control is almost non-existent. Then it must be created again, given another code, and sent to Regulatory Affairs for updating and storage in their database. This is just one example of how the current workflow is inefficient. While distribution can be done electronically with the system, it is far from paperless in terms of revisions or version control. Finally, a hard copy must be entered in the Regulatory Affairs' database since it is the final storage of all documents.
Compilation for large submissions, such as NDAs, is also done by Regulatory Affairs. It is handled by the submission group of the department and guided by a project leader. Yet again, different systems are used. The electronic images are stored by archive in an image database. This system stores every page of every document as a single image. Therefore, if a document is 5,000 pages long, it consists of 5,000 images, which are not accepted by the FDA. Thus, the submission group must compile all necessary documents for every submission. This was formerly done (and for some types of FDA correspondence is still done) with paper copies. However, for electronic submissions, special steps must be taken. Submission must use yet another system to convert and compile all needed documents. This is usually done by manually scanning each final version into PDF format, but can also be done by converting the image files to PDF. The FDA requires the PDF format for the final published document. The main drawback to converting the image files to PDF is that the validated conversion only allows 50 images (pages) to be converted at once. The sections for each of the submissions are then stored until they are ready to be published. Once this is done, the electronic medium of choice (digital tape if the submission totals more than five full compact disks) is selected; the relevant data is stored, and sent to the FDA (Supporting pharmaceutical research and development, 2001; Shortening Time to Market Through Innovation of Regulatory Approval Process, 2002).
Like its competitors, Purdue Pharmaceutical and Boots Healthcare, the implementation of Documentum, a validated system that allows for version control and audit functions, has been a complex and critical undertaking for Bayer Pharmaceutical. It is especially important in the integration of information technology and corporate goals. These goals include bringing compounds to market faster, improving Bayer's competitive advantage through time and cost savings, flexibility and management of content, global collaboration and improving the efficiency of the administrative aspects of the business. As stated earlier, the current systems used do not interact nor allow for the paperless workflow that is key to this desired efficiency. Documentum is a tool that handles all content management needs and allows compliance with the increasing demands of FDA requirements via its open standards-based architecture that allows easy integration of content management with its SAP applications. In addition, Documentum supports XML (eXtensible Markup Language), allowing disparate systems to be linked together and facilitates the movement of information between them in an automated fashion. With the complete rollout of Documentum scheduled for early 2003, Bayer should realize greater efficiency. Documentum uses linked documents allowing the reader to view a reference to specific page by clicking on the link rather than manually finding the correct volume and page on which the reference is printed (Documentum in the Pharmaceuticals Industry, 2002).
The use of Adobe Acrobat and PDF files makes the process quick and easy. (U.S. Food & Drug Administration Speeds Review of New Drug Applications with Adobe Acrobat and PDF, 2002). The only problem occurs when the document is changed and the links and table of contents need to be updated. Thus, a paperless flow of information and a single powerful, integrated tool which replaces many independent systems is the direction that the Regulatory community needs to head in order to achieve success and increased efficiency. This is especially important since Bayer has only done one other electronic NDA, that being Avelox™ last year (NDA Approvals for Calendar Year 2001, 2001).
Since Documentum is a completely validated system, it meets the FDA's stringent auditing requirements. It offers version control and security attributes that current systems simply do not have. It will be possible to electronically log those who view and/or access the document, something the FDA requires be done. It will allow for an electronic environment throughout the entire Pharmaceutical division. For example, if the scenario described above were to occur in a Documentum environment, efficiency would be greatly increased. The investigator in the field would simply create his application using a standard template similar to the many paper variations used today. The Investigational Review Board could electronically approve this document. The research associate at the investigator's site could then place the document in Documentum, which would automatically give it an archive number. The document would then be routed automatically per standard operating procedure guidelines to the proper people. Electronic review and signatures would then be applied to the document. Simultaneously to this, the FDA liaison in Regulatory Affairs would be able to monitor the progress and view any revision until the point where the approved, completed document would be finalized by the liaison and readied for publishing. It is a streamlined, efficient process that will increase productivity and improve results. A list of everyone that revised or viewed the document can be generated electronically, replacing the cumbersome logbooks of the existing system (Shortening Time to Market Through Innovation of Regulatory Approval Process, 2002; also see Appendix B).
There are many challenges in the achievement of this transformation. First, training all the users and making them comfortable with the new system is a large undertaking, especially within a company of Bayer's size. There are also many logistical problems and geographic concerns. It has taken the German-based organization quite some time to realize this fact, but it has finally taken action, not only by the American-based Bayer Corporation, but also by the entire health sciences division of Bayer AG. Getting the pharmaceutical counterpart in Europe to agree to this new system will also be a challenge, since Germany is currently much farther behind in electronic submissions. A global submissions group could alleviate any shortcomings the German counterparts are experiencing (Bayer's high-tech pharmaceutical research platform, 2001).
With the company-wide top priority being the timely submission of NDAs in a complete, validated and electronic format, the most current challenge facing information systems is implementation on the move. Since there is no time for trial and error, precise forward-thinking decisions must be made. There is still much to be learned because any unknown problems will have to be dealt with as they arise. Bayer's profitability and long-term survival is at stake.