Features

Lifecycle Tracking In Analytical Laboratories

Continuing our series on 21CFR11 compliance

August 22, 2005

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 eighth 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 is presented here as just one example of an application that can be developed based on Part 11. There are many other useful commercial applications currently available.

Table 1: Part 11 Requirements
Requirement	Citation	Description
Validation	11.10a, 11.30	Computer systems must be methodically validated to ensure accuracy, reliability and consistency with intended performance.
Audit Trails	11.10e, 11.30	Systems must provide secure, computer-generated, time-stamped audit trails to record actions that create, modify or delete electronic records.
Record Retention, Protection, Reproducibility and Retrievability	11.10b, c	Systems must have capability to retain, protect and readily retrieve records throughout the established retention period. Systems must be able to produce, intact, all records stored electronically, in both human-readable and electronic form.
Documentation Controls	11.10k	Controls must exist over access to, revision of, distribution of, and use of documentation for system operation and maintenance.
Open systems	11.30	Systems must provide special security measures, such as encryption for systems that can be accessed by outsiders.
Security	11.10d, i, j, 11.30	Systems must limit access to only authorized, qualified personnel. Written policies must be in place, which hold individuals responsible for actions initiated under their electronic signatures.
Electronic Signature	11.200a 11.300d	Systems must provide measures to ensure that use is limited to only genuine owners and that attempted use by others is detected and promptly reported. Systems must employ two distinct identification mechanisms (username/password). Both username and password must be entered before a signing session and at least the password is entered at each subsequent signing during the same session. Electronic signatures must not be reused or reassigned. The purpose of an electronic signature purpose must be clearly indicated. Finally, systems must include measures to prohibit falsification of electronic signatures by ordinary means.
Certificate to FDA	11.100c	Written certification must be provided to the FDA Office of Regional Operations that all electronic signatures in use are the legally binding equivalent of traditional handwritten signatures.

The functionality in ExyLIMS that we will focus on in this article will be waste tracking and disposal. This process centers on the lifecycle of the waste container:

• Login of the waste container
• Disposal of items to the waste container
• Sampling the waste container to determine disposition
• Disposition of the waste container
• Organization of all shipping documentation including manifest

Figure 1: Location of Waste Node in ExyLIMS

The first step in this process is to navigate to the appropriate location in ExyLIMS. The ExyLIMS graphical user interface is based on an outline format in which the user drills down from general to specific topics. This is also known as a tree view of the data. Waste handling is located in the Logbook tab under the heading of Waste. As seen in Figure 1, Waste is organized according to Active and Inactive waste containers. Active containers are permitted to accept items and generalized waste. Inactive containers have been dispositioned and are no longer on site. Inactive containers are no longer editable, with the exception that documents may be added such as manifests from the waste hauler.

A left mouse click on the Active node of the Waste tree sets the focus for a new waste container login. A right mouse click then presents the user with the menu choice ‘New Waste Container.’ A user choosing this selection will be presented with the screen depicted in Figure 2. A unique ‘WA’ number will automatically be generated to identify each new waste container. This number along with other information supplied at login is used to generate a bar coded label for the waste container. Please see Figure 3 for an example.

Figure 2: Waste Container login

The first choice for the user when logging in a waste container is to identify the class of the waste. Please see Figure 4 for an example of waste classes used at the author’s site. This list is configurable and can be modified at any time to suit the needs of the facility. Other fields to be filled in on login include type of receptacle (e.g., drum), volume (e.g., 55) and units (e.g., gallons). The creation date/time is automatically entered based on the system date. Once these data are entered, the user can press the commit button to save and create the waste container.

Figure 3: Waste Container label

Waste containers may be used in either of two complimentary ways. The first mode is useful for commonly used laboratory solvents such as methanol and acetonitrile. In this example, solvents are used throughout the laboratory in various solutions, mobile phases, and extractions. The waste is collected in intermediate collection bottles and then transferred to the waste container logged in above. In this example, individual solvent and solution tracking numbers are not recorded.

Figure 4: Waste Class selection

The second mode for using waste containers is to track each individual item as it enters the waste container. Items can include the following:

• Sample Containers
• Standards
• Reagents
• Solutions

Sample containers are tracked at the author’s site to ensure proper handling of the samples from cradle to grave. Samples are typically logged in, analyzed, reported and properly disposed. Proper disposal of samples (e.g., not in the municipal landfill) can be of particular concern to clients of the laboratory as it is ultimately their responsibility to assure proper disposal.

Figure 5: Adding items into the Waste Container

Additionally, laboratories, from time to time, must prepare special waste containers also known as lab packs to deal with particularly hazardous or non-routine materials. Tracking any standards, reagents, or solutions that may go into this waste container makes good sense from a health and safety standpoint. It also aids in preparing the manifest. An example of items being scanned into waste container ‘WA0000001’ is given in Figure 5.

Figure 6: Containers out for Testing

In addition to adding items to the waste container, containers can also be taken out. Please see Figure 6 for an example. This provides the user with the ability to remove samples from the drum to do further testing to determine disposition. For example, a particular waste hauler may charge two different rates depending on the BTU value of the waste. This functionality links the “containers out for t esting” to the sample login where the container is logged in for BTU content, is tested, and a certificate of analysis is generated. This certificate of analysis can then be presented to the waste hauler.

Once a waste container is ready for disposal, the Dispose button is pressed (see Figure 7). This activates the lower portion of the waste container screen and prompts the user for the following additional information:

•	% Full – any value from 0-100.
•	Disposition Date – automatically filled by system time
•	Disposition – configurable list (e.g., waste hauler)
•	Waste Hauler – pick list of available vendors
•	Manifest Number

Figure 7: Disposal screen

Committing the disposal button transfers the waste container from the Active node to the Inactive node of the Waste tree (see Figure 8). At this point all fields become non-editable for that waste container with the exception of the documents node. The location of this node can be seen in Figure 9. The documents node is to

Figure 8: Waste Container transfer from Active to Inactive

be used to capture any documents associated with the waste container including waybills, manifests and certificates of analysis. These documents may be added whether the container is active or inactive. The primary reason this functionality is offered in the Inactive area is to provide a means to attach final waste hauler manifests, many of which are received more than six months after waste pickup.

Figure 9: Additional Nodes to Waste Containers

An example of a document attached to waste container ‘WA0000001’ is given in Figure 10. As noted above, as many documents as necessary can be attached. Also noteworthy in Figure 10 are two other nodes under waste container ‘WA0000001’: ICOC and Items. The items node is simply a graphical representation of the items scanned in as described above. The ICOC (Internal Chain of Custody) node is used to give the location of the waste drum. The functionality of the ICOC module in ExyLIMS was described in a previous article. It is sufficient to say at this point that the current location of the waste container is given along with any previous locations that it may have had.

Figure 10: Expanded documents, ICOC and Items Nodes

Waste tracking and disposal 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.