Achieving GLP Compliance Through Deployment of LIMS

In 1997, the Organization for Economic Co-operation and Development (OECD) published the revised principles of Good Laboratory Practice (GLP) to regulate the non-clinical safety testing of test items contained in pharmaceuticals, pesticides, cosmetics, veterinary drugs, food and feed additives and industrial chemicals. These test items are frequently synthetic chemicals, but they may also be of natural or biological origin and, in some circumstances, may be living organisms.

The purpose of the principles of GLP is to promote the development of high quality, validated test data. Comparable quality and validation of test data forms the basis for the mutual acceptance of data among countries. If individual countries can confidently rely on test data developed in other countries, duplicative testing can be avoided, thereby saving time and resources. The application of these principles should help to avoid the creation of technical barriers to trade and further improve the protection of human health and the environment.

GLP is a quality system concerned with the organizational process and the conditions under which non-clinical health and environmental safety studies are planned, performed, monitored, recorded, archived and reported. Non-clinical health and environmental safety studies covered by the principles of GLP include work conducted in the laboratory, in greenhouses and in the field. These studies are undertaken to generate data on the properties of test items and assess the hazards and risks to users, consumers and third parties, including the environment. GLP helps assure regulatory authorities that the data submitted are a true reflection of the results obtained during the study and can therefore be relied upon when making risk/safety assessments for the purpose of registering or licensing pharmaceuticals, pesticides, cosmetics, veterinary drugs, food and feed additives and industrial chemicals.

Work that does not constitute a regulatory study is not required to be conducted in compliance with the principles of GLP. For example, work undertaken by Quality Control (QC) laboratories in support of final product release or laboratory work in support of human clinical trials do not require to be conducted in compliance with the principles of GLP.

The principles of GLP require that study plans, raw data and final reports should be systematically archived for secure record keeping, reporting, storage and retrieval. Archive design and archive conditions should protect contents from untimely deterioration. All data generated during the conduct of the study should be recorded directly, promptly, accurately and legibly. Any change in the raw data should be made so as not to obscure the previous entry, should indicate the reason for change and should be dated and signed or initialed by the individual making the change.

The Need for LIMS

Manual capture, calculation and verification of raw data result in a tremendous drain on human resources while also jeopardizing the integrity of the information. The administration of paper records is particularly inefficient and expensive and data cannot be easily integrated with other technologies employed by the organization. As a result, complying with the strict principles of GLP can prove a very time consuming and expensive process.

There emerges a need to employ sophisticated, enterprise-wide Laboratory Information Management Systems (LIMS) capable of addressing the complexity of the regulations, ensuring compliance with current best practice and satisfying the concerns and expectations of the regulators.

Data generated from an instrument electronically and captured as a direct computer input can be identified at the time of the input by the individual(s) responsible for direct data entries. An efficient computerized system design always provides for the retention of full audit trails to show all changes to the data without obscuring the original data. It is also mandatory to associate all changes to data with the persons having made those changes by use of timed and dated electronic signatures. The justification of changes can be also recorded and saved with each entry.

LIMS solutions can also generate the final report of the study automatically providing a comprehensive description of the methods and materials used and a presentation of the results, including calculations and determinations of statistical significance.

Validation

When it comes to computerized systems, the principles of GLP also demand the existence of relevant validation documentation. This is because a validated system ensures accurate results and prevents fraud as well as failure of the system.

Validation costs vary enormously even within the same industry. These can range from 5% of the total project cost for a multi-site, worldwide, industry standard Enterprise Resource Planning (ERP) central server deployment to up to 75% of the total project cost for a bespoke customized system. In general, validation costs are higher when it comes to the implementation of one-off systems, new technology or complex applications. On the contrary, validation costs are lower for multiple rollouts of the same system, or when Commercial Off-The-Shelf (COTS) solutions are employed that have been specifically designed to meet industry standard GLP requirements. In conclusion, best validation practice constitutes spending between 15 and 25% of the overall project cost.

Cost-Effective Validation StrategiesOne of the most cost-effective validation strategies is to follow the Good Automated Manufacturing Practice (GAMP) Guide for Validation of Automated Systems. The Guide draws together key principles and practices and describes how they can be applied to determine the extent and scope of validation for different types of automated systems. The principles of GAMP concern five different software categories, namely operating systems, hardware and instrument embedded software, COTS, configurable systems and customized LIMS. Following the Guide provides significant cost benefits by aiding the production of systems that are fit for purpose, meet user and business requirements and have acceptable operation and maintenance costs. The time and effort taken to achieve compliant systems is also reduced and compliance with regulatory expectations is improved by defining a common and comprehensive life cycle model. Thermo Fisher Scientific offers purpose-built or COTS solutions -- such as Darwin LIMS™ for pharmaceutical manufacturing R&D and QA/QC and Watson LIMS™ for Bioanalytical laboratories -- to reduce the complexity and risk of system validation.

In order to achieve validation with the minimum cost possible while also speeding up the whole project, organizations should purchase validation services only from experienced providers. The ideal vendor should be fully aware of the GLP regulations, the principles of GAMP, the validation needs of the specific application area as well as the operation and usability of the specific application software that needs to be validated. Additionally, the vendor should possess relevant information technology expertise and be knowledgeable of validation industry best practice. Finally, the vendor should comprehend the internal validation procedures of the specific organization.

Effective, timely validation can be most effectively accomplished by a validation team that has been thoroughly trained through a course that brings together the different experiences of validation approaches of the team members so that everybody agrees a common approach. Furthermore, cost-effective validation can be achieved via standardization of a single LIMS solution across all laboratory facilities of an organization or via rollout of the same system sequentially. Following one of these strategies will greatly reduce validation costs as a percentage of the overall project expenditure since only minimal acceptance testing is needed at every site and most testing can be cross-referenced.
Risk analysis may be also used but always with caution. It is true that many GLP laboratories process low risk records, however only functions, not records, can be validated. In the LIMS area it is common for the same generic functions to be used across all records, whether high or low risk. Therefore all functions must be considered high risk and subject to full validation. It can be more efficient to conduct a high-level risk analysis of the entire LIMS, which acknowledges that the whole system is high risk, rather than conduct a detailed risk analysis of every function which eventually reaches the same conclusion, but with more effort(1).
Organizations should also make appropriate use of the testing that the vendor has already carried out. For this reason, they should consider purchasing a vendor-supplied validation kit and also avoid validating functionality which they do not intend to use.

Finally, organizations should ensure that the validated state of the systems is maintained. The principles of GAMP define that this is achieved by ensuring that existing operational procedures are kept up-to-date. Maintenance of the validated state is primarily the responsibility of the system owner, and is typically achieved by defined service-level agreements with, for example, the IT function. For COTS, the vendor support package is also a vital component of the overall system maintenance.

Summary

Compliance with the principles of GLP is of high importance when registering or licensing pharmaceuticals, pesticides, cosmetics, veterinary drugs, food and feed additives and industrial chemicals. LIMS solutions have emerged as the most appropriate tool to assist towards compliance with the principles of GLP. Such systems can efficiently and safely record, report, store and retrieve study plans, raw data and final reports, thereby addressing the complexity of the regulations.

In order to comply with the principles of GLP, LIMS solutions need to be fully validated. This may be a particularly expensive process but costs can be considerably minimized by following certain strategies; adhering to the principles of GAMP, sourcing validation services from experienced vendors, employing a consistently trained validation team, standardizing on a single solution and ensuring long-term maintenance of the validated state of the systems.

References

“Risk Analysis Warning – your validation costs may go up as well as down;” John Dickson, Thermo Fisher Scientific, Technical Presentation, Pittcon 2004.

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