Ask a group of scientists to consider a laboratory computing solution and, providing their experiences have not been too negative, they will instinctively think of data acquisition and storage. However, increasingly systems such as LIMS (Laboratory Information Management System) are becoming key drivers in enforcing the laboratory's Quality Control and Quality Assurance procedures. This is a natural progression, since the majority of analytical activities in the modern laboratory are undertaken to support the process control function, of which QC is a significant element. Recent advances in information technology, together with the functional maturity of modern LIMS products, are presenting users with new opportunities to facilitate QA/QC through the automation of activities such as:

• Data entry from instrumentation
• Test result data specification checking
• Assignment of laboratory activities and workload
•  Management analysis and reporting

• Laboratory personnel qualification and training
• Labeling, storage and expiry of reagents, solutions and hazardous chemicals
• Equipment documentation, calibration and validation
• Integration of laboratory instruments and systems
• Sample Labeling and Tracking
• Standard Operating Procedures (SOP’s) and their use
• Analytical method validation and documentation
• Computer software validation
• Documentation of deviations from laboratory procedures
• Determination of all appropriate QC controls
• QC controls are concerned with the actual day-to-day quality of analytical data produced. The activities are mainly centered on comparison of data with pre-established specifications and acting and reporting on the results of the comparison.

Within LIMS it is possible to define individual laboratory personnel and to specify their particular working environment, with respect to activities they can undertake and data to which they have access. For example, defining the LIMS function menu items that are available to each user (functions such as 'Login a Sample', 'Enter Analytical Results' and 'Produce Certificate of Analysis'). In regulated environments, only certain users are allowed to carry out tests or use specific instruments for entering and determining results. LIMS have facilities to allow users to be approved to perform specific functions. Access can be limited to the dataset that the laboratory user needs to fulfill their job function. For example, only users in the microbiology laboratory can be given access to analytical methods and worksheets concerned with the testing for micro-organisms.

LIMS can automate the production of a bar-code label when a sample is logged in and allow the definition of storage information such as location and storage conditions against the logged in sample. LIMS enable the tracking of all instruments, systems (such as CDS - Chromatography Data Systems) and equipment used within the laboratory. In the case of instrument calibration and servicing periods, LIMS can be defined to automatically flag and remove from operation instruments that require periodic servicing and calibration

• Once analytical methods are defined in the LIMS, it is possible to store the complete method description against the LIMS entry. Each method can be versioned to reflect changes through time and to assure that only the most recent method is used. An authorization cycle can be applied to an analytical method so that review and approval by different individuals is enforced before the method is utilized.
• Deviations in laboratory working practice or analytical data can be raised within the LIMS for tracking and reporting purposes. A powerful feature of some LIMS is the ease with which users are able to record and manage unforeseen events which inevitably occur in a busy laboratory. Examples of this include robot failure or a sample breakage. Depending upon the system’s configuration, the entry of such an ‘incident’ can be tracked, reviewed and the creation and transmission of reports to laboratory supervisors can be automated. To satisfy regulatory requirements, such functionality should handle incidents with a full life-cycle, including checklist completion and authorization.
• LIMS can be integrated with all major instrument types in the laboratory, in order to more quickly process results and to reduce user-transcriptions errors inherent in all manual entry processes. Modern LIMS functionality includes audit-trailing mechanisms to record, track and provide justification for changes to all laboratory data (who, what, why, when and where). Rather than limiting auditing to just pre-defined items such as samples and results, some LIMS are now able to permit the auditing of any item, e.g. instrument or operator records. If required, the activation of an audit can automatically trigger the sending of notifications to key personnel. Data querying capabilities are also now available as part of auditing functionality which allows users to data mine a result and examine all previously audited values.

More specific QC controls can be implemented within the LIMS to allow for efficient control of analytical data:

• LIMS allow specifications to be entered for each analytical result type. Analytical results failing to conform to specification flag a warning to the users and also allow a deviation or incident to be raised and stored against the result type. More advanced LIMS offer a variety of definable 'out-of-spec' warnings which prompt for a variety of responses, dependent upon their significance.
• LIMS are able to define a wide range of laboratory QA/QC samples and add them to worksheet runs (such as blanks, calibrations, controls, calibration checks, washes and spikes) and be able to compute and report QA/QC calculations. Modern LIMS can build up and save complex calculations to take a variety of data inputs into calculations, such as results or other sample data.
• When laboratory standards are defined, the LIMS is able to define automatic expiry of the standard based upon usage and/or time.
• Some LIMS allow for the automatic production of statistical quality control (SQC) charts to support the QC process through time. SQC charts include standard types (such as Shewhart, Process Capability and CuSum) and trend analysis is available to be performed on charted data.

Electronic records

Of growing concern to an increasing number of regulatory agencies is the need to assure more effectively that electronic data submitted to regulatory agencies is:

• trustworthy
• reliable
• authentic and legal

This reflects the increasing importance of e-commerce and the need to circulate laboratory data via the Internet. One example of how this requirement is affecting the pharmaceutical industry is through the US Food and Drug Administration (FDA) ruling 21 CFR Part 11. In pharmaceutical industry laboratories, the effect of this ruling has been profound and, according to some estimates, compliance is likely to cost five times as much as Y2K. As more industry sectors move to similar ways of working, requirements for these types of controls are likely to become more widespread. The US Environmental Protection Agency is about to introduce its own ruling on electronic record-keeping requirements, entitled CROMERRR (Cross-Media Electronic Reporting and Record-keeping Rule). This is anticipated to have a similar impact in the environmental arena as 21 CFR Part 11 did on the pharmaceutical industry. The specific requirement for good record keeping practice and electronic signature mechanisms require LIMS vendors to address several areas of LIMS functionality. In order to achieve compliance with 21 CFR Part 11, as a minimum LIMS need to provide:

• a means for specific identification of regulatory data with the laboratory
• audit trail mechanisms for regulatory data
• security controls on the data (from a logical, functional and data perspective)
• mechanisms for electronically signing regulatory data entries

The obvious impact that 21 CFR part 11 is having on LIMS vendors and pharmaceutical industry customers is that it is encouraging closer co-operation to develop solutions that are in full compliance with the Rule. There is still a variance in the Rule's interpretation among different pharmaceutical companies. As the pharmaceutical industry's (and indeed the FDA's) familiarity with the implementation of the Rule increases then a more definitive set of requirements will evolve and become best practice.

Summary

The regulatory requirement for measures to ensure quality control in modern analytical laboratories varies according to industry, the laboratory's geographic location and the analytical methods it employs. Nevertheless, without operating an automated control mechanism, all laboratories intent on fulfilling the requirements of GLP compliance and, therefore, assuring that effective QA/QC practices are in place, face an onerous task. A LIMS is such an automated mechanism, providing a secure framework for the input, processing and reporting of information such as test results, samples and methods. However, the implementation of a LIMS is by no means the whole solution. It must be supported by sound knowledge of regulatory requirements and comprehensive QA/QC procedures, which are both documented and defendable. Perhaps of increasing significance is the role modern LIMS can play in helping laboratories to comply with changing regulatory requirements, such as 21 CFR Part 11.