In 1997 the U.S. Food and Drug Administration, in response to requests from industry, issued a regulation specifying criteria for the acceptance of electronic records and electronic signatures as the legal equivalent to manual, paper based systems. The citation for this regulation can be found in the federal register at 21CFR11.
This article is the ninth in a series on Part 11. Previous articles have focused on defining and explaining the regulation. For a brief summary of Part 11 requirements, please see Table 1. This article will build upon these foundation concepts as we move away from the pedantic nature of the CFR and focus in on a real world application, ExyLIMS. ExyLIMS is a client-server based program written at the author's site to help the analytical laboratory comply in an FDA-regulated environment. It is important for the reader to understand that the ExyLIMS example presented here is just one example of an application that can be developed based on Part 11. There are many other useful commercial applications currently available.
The functionality in ExyLIMS that we will focus on in this article will be electronic document management. Successful document management in a laboratory setting requires, at a minimum, proper procedures for the following events:
At the author's laboratory, it was decided that the best way to implement an effective document management program was to make the entire process electronic. Several synergisms can be realized by doing this. First, version control and change control can easily be enforced electronically. Each time a new document is created, it receives a unique document identification number (DIN) and a version number. Each time the document is revised, the DIN remains the same and the version number is incremented. This maintains the thread to the original document and also conveys the new version. Further, old versions of the document are not displayed in the active published area so that only the current version is available.
Change control can also be better controlled electronically. As mentioned above, new versions can be created and tracked. Taking this one step further, security roles can be created to allow, for example, only supervisors to be able to create new versions of documents. Additionally, once created, new rules can be created to ensure that proper review and authorizations for the documents are conducted.
Finally, and most importantly, is the issue of distribution. This is where electronic document management really shines. Most laboratories manage their standard operating procedures (SOPs) in a paper-based system. This means that when a new version comes along, someone has to go throughout the organization and replace the old document in each SOP manual. Two main issues arise. First, the time it can take to do this replacement can be substantial. The more important issue, though, is to make sure that every single occurrence of the old document has been replaced.
It is a frequent FDA-483 observation that out-of-date SOPs are found in the laboratory. The issue arises from people making copies of SOPs to have at their desk, or at the laboratory bench during analysis, or anywhere that they can't or don't want to bring the typically bulky SOP manual. The real danger is that these obsolete SOPs are being used for regulated FDA studies. In the worst case, this is a situation that can potentially undermine public health.
An electronic document management system avoids these pitfalls because the final published electronic document is the official document. Once an electronic document is printed all controls on that document are lost, such as reproduction, updating, distribution and storage. Therefore, keeping the document electronic is compelling. It also makes distribution much easier as the most current version of any document can easily be found on any user's desktop PC or a publicly assigned workstation. Further, these electronic procedures can now be embedded and referenced in the LIMS (Laboratory Infor-mation Management System) itself. For example, extraction procedures can be called up for review during the batch processing of samples. Health and safety procedures can be quickly accessed during bulk solvent handling. There are many other examples where electronic documents can be added to a process to provide instant access to SOPs that provide guidance and enhance a given process.
Finally, it should be noted that there are many commercial electronic document management packages available today. The author spent a considerable amount of time evaluating these packages and concluded for his organization that a homegrown approach was appropriate. This is based primarily on the requirement of very tight coupling between the document system and the laboratory's LIMS system, ExyLIMS. The main requirement for ExyLIMS is to provide a workspace so that all aspects of the laboratory can be performed.
A secondary consideration is the cost and complexity of commercial systems. These systems can be very costly and require significant Resources to implement. The bottom line is that the system described below is relatively simple, relatively cheap, and integrated to the lab's LIMS. Other users and sites may have divergent requirements and so a commercial system may be more appropriate. The important point in this article is that, no matter which type of system is chosen, the key concepts discussed below are necessary for any implementation of successful electronic document management.
The second key concept centers on the five stages in the lifecycle of the electronic document and will be further described in detail below:
The draft stage of an electronic document occurs when a new document is created or an
If the Routing Checkbox is selected, draft review and final approval will be serial. For example, in the case where there are three reviewers, User 3 may not review the document until User 2, and User 2 may not review until User 1 has completed his or her review. Alternatively, if the box isn't checked, persons may review the document in any order.
By default, ExyLIMS converts Microsoft Office documents to Adobe Acrobat PDF. The main advantage to doing this is to add security to the document. For example, security can be configured to disable cut, copy and paste functions as well as content modification. If, however, the user requires the document to stay in its native format (for example, a form to be filled out), simply check the Final Documents Unlocked Checkbox to disable conversion.
Finally, any documents that are related, referenced, or are dependent on the newly created document can be added to the Dependencies tab as shown in Figure 6. This tab provides a convenient one-stop location that can be used to determine what affect changes to one document may have on others.
Once all the fields are filled out and the document is committed and electronically signed, it is placed into the Documents in Progress tree under the category in which it was created (see Figure 7 for an example). Here, the Pest Control SOP is displayed with a unique DIN, 'V0000009', along with a '-1' which indicates that this is version 1. Also displayed is the current stage of the document. In this example, the document is in the draft stage.
Once all the draft reviews are finished, the document automatically moves on to the revise stage. The revise stage gives the author the opportunity to consider the comments solicited in the markup stage and incorporate them into the document if he or she sees fit to do so (see Figure 11 for an example). Once the document has been revised by the author, he or she presses the Commit and Promote button which moves the document on to the Final stage.
During the Final Stage, final approvers get to review the final document and must answer two questions. As seen in Figure 12, one of the pieces of data to be entered is the Reviewed checkbox. After each final approver reviews the document, he or she must check this box to acknowledge that the document was reviewed. Additionally, he or she must either check or not check the reviewed checkbox. If all final approvers check both the reviewed and approved boxes, the document will automatically move on to the Published stage. If any of the approved boxes are not checked, the document will not advance and the author will be prompted to re-version the document and start the entire process over again.
Once the document makes it through the Final stage, it is queued for publishing. If the 'Final Document Unlocked' box is not checked as described above, the document will be converted to an Adobe Acrobat file (see Figure 13) and moved to the Published Documents area of the electronic library as seen in Figure 1. If the 'Final Documents Unlocked' box is checked, the document is moved to the Published Documents area, but is not converted to PDF. Once the document is published, not only is the final stage published, but also all stages of the document are maintained, and with the proper security permissions, can be reviewed as seen in Figure 14. Therefore, the entire evolutionary thread of the document is maintained.
Periodic Review and Versioning
Periodic Review and Versioning can both be initiated by selecting the document in the Documents Published section of the electronic library and right-clicking with the mouse to expose the right-click menu as seen in Figure 15. Documents that need review are depicted by an icon that turns from all green to mostly green with a yellow stripe one month before expiry. Once the document has expired the yellow stripe turns red. This provides a visual queue to the user that a review is required. Selecting the 'Periodic Review' right-click menu option completes review. The user is then prompted to enter an electronic signature to complete the review.
If versioning is required for a document, the user selects the 'Version' right-click menu choice and is presented with the dialog box seen in Figure 16. At this point the user may cancel the operation, edit the existing document if changes are minor, or attach a new document if major changes are required. Once the changes have been affected, the DIN remains the same, V0000009 in our example below, and the version number gets incremented. In our example above the new version would be numbered V0000009-2.
Electronic document management is another example of a successful application based on Part 11 compliance. Part 11 requires electronic records and electronic signatures to be secure, authentic and validated. This requirement alone, of course, does not ensure a valuable application for the laboratory. However, once these basic Part 11 requirements are met, sophisticated software applications can be created that can greatly enhance laboratory productivity and FDA compliance.
21CFR11: Electronic Document Management
Continuing our series on 21CFR11 compliance
By Kevin Lloyd
blog comments powered by Disqus