Since the FDA first introduced Quality by Design (QbD) principles to the pharmaceutical industry a decade ago, laboratories have been hard at work developing process-based methodologies for ensuring product quality. Because these methodologies enable labs to detect problems earlier and limit damage caused by production errors, the industry has embraced them enthusiastically. There’s a downside, however: monitoring entire production processes, from raw materials to finished product, generates data of a far greater magnitude than older systems that analysed only the end product.
Today, a laboratory’s informatics system directly correlates with the overall quality and the safety of the products that a pharmaceutical company manufactures – an inefficient lab system is detrimental to the business. Without a highly integrated and as close to paperless as possible informatics system in place, the lab cannot play a meaningful role in rooting out production inefficiency. With a tightly integrated laboratory, however, management can rely on the lab as a quality assurance hub, capable of identifying substandard products at many points in the process and, ideally, before they even occur.
Modern laboratory informatics
In-process error detection can significantly reduce the frequency and severity of product quality problems, but only if the lab uses an informatics solution that pushes data to lab managers when and where it is needed. An integrated informatics system enables pharmaceutical manufacturers to closely manage quality and drive continuous process improvement across an entire enterprise. A comprehensive laboratory informatics solution consists primarily of three interconnected systems: a lab execution system (LES), a scientific data management system (SDMS) and a laboratory information management system (LIMS).
Without a highly integrated and as close to paperless as possible informatics system in place, the lab cannot play a meaningful role in rooting out production inefficiency
An LES plays a critical role in minimising human error within the lab by ensuring that staff properly execute all procedures. It automates these standard operating procedures (SOPs) in a step-by-step fashion, enabling even newly trained laboratory professionals to consistently and safely carry out routine steps. The LES can also document any deviations from standard procedure for future staff training or external review by auditors. By standardising and centralising SOPs for all staff activities, from sample preparation and analytical testing to instrument calibration, an LES ensures consistency that is critical to labs that follow Quality by Design (QbD) principles for rigid quality control.
An SDMS focuses more on the data itself. It automates, standardises and centralises data collected from instruments across one or more labs. This removes the need for paper entirely, taking human transcription error out of the data collection and reporting process entirely. Moreover, the SDMS allows users to retrieve any data at any point in time, and in its original form, without having to revisit the original instrument files or paper-based archives. In a paper-based environment, it is estimated that three out of every thousand manual data transcriptions contain errors, and this can increase to three in one hundred in more stressful or complex environments. Manual transcription errors cannot exist in labs that rely on an integrated informatics system.
An SDMS also functions as a single archive for all incoming laboratory data regardless of their original form. For later retrieval, instrument data can then be normalised, using common languages such as XML, where it is easily accessible to all users, even non-technical people who can review, parse and transmit the data in whichever formats are necessary. These data collection and review capabilities are a critical part of any QbD system.
The LIMS has traditionally been the workhorse for managing samples, tests and results, but today’s LIMS are capable of much more
The LIMS, the final piece of the modern laboratory informatics triad, has traditionally been the workhorse for managing samples, tests and results, but today’s LIMS are capable of much more. When fully integrated with a lab’s SDMS and LES systems, a modern LIMS gives lab management a powerful dashboard from which they can manage resources, identify unexpected data, track instrument maintenance and calibration schedules, monitor operations and view the entire lifecycle of their product.
Working together, the LIMS, SDMS and LES create a truly paperless lab that transforms the ever-increasing complexity of the modern pharmaceutical laboratory into opportunities for increased productivity, efficiency and quality.
Challenges in the modern lab
Large molecule drug production, a rapidly growing segment of the industry, is one example of increasing production complexity and the need for better software to manage it. Even minor changes in manufacturing processes for biologics can cause significant changes in efficacy or immunogenicity.
Large molecule drug production commonly involves critical steps such as formulation stability testing and chromatography testing for purity and content uniformity. Furthermore, the introduction of living organisms into drug development and production requires continuous environmental monitoring to ensure the health of developing cell lines that are extremely sensitive to even small changes in environmental pH, temperature and other factors. Even slight deviation can kill micro-organisms, ruin a batch and halt drug production.
An integrated LIMS helps to simplify regulatory compliance by storing data in a centralised, standardised repository where it can be used for compliance in different geographies
With an integrated and paperless informatics system, data from constant monitoring of environmental conditions can be easily transmitted to relevant lab staff in near real time. Having these data when and where they need them, all managed within a centralised system, allows technicians to intervene quickly when processes are dangerously out of specification. This can often mean the difference between a successful batch and a failed one.
Modern pharmaceutical companies also face increasing regulatory oversight, a challenge that becomes even greater when their products are sold in markets globally. Complying with regulatory requirements and meeting international standards such as ISO 17025 can be time-consuming, and without a system of record to manage this, commercialisation can stall, costing a manufacturer billions. An integrated LIMS helps to simplify regulatory compliance by storing data in a centralised, standardised repository where it can be used for compliance in different geographies – streamlined data export to a regulatory dashboard makes this easy and efficient. The chances of a costly bottleneck in production or manufacturing are minimised.
The importance of integration
In the past, many labs treated their SDMS, LIMS, and LES as separate systems, and communication among them required integration of multiple software types and validation of those individual and integrated solutions, creating a time-consuming and costly scenario, in addition to creating more layers of maintenance and support required for those disparate systems over time. This is no longer tenable as lab operations become more complex and distributed. Integrating these systems into a single informatics platform increases their value significantly – in short, the whole is more than the sum of its parts.
The ability to monitor, manage and review all laboratory processes and data in a single, tightly integrated solution allows lab management to streamline operations and minimise the costs of complexity, such as maintenance, regulatory compliance, human error and validation. Systems such as Thermo Scientific SampleManager LIMS offer this integrated capability, including built-in functionality for LIMS, SDMS and LES. It also integrates seamlessly with enterprise management solutions such as enterprise resource planning (ERP) systems and manufacturing execution systems (MES) for comprehensive, enterprise-wide visibility and management.
Integrating these systems prevents breakdowns at three critical points in the lab: data capture, data transcription and data management. Standardised, step-by-step SOPs from the LES reduce the potential for human error during data capture processes. The SDMS standardises data transcription and recording across the entire organisation, virtually eliminating the potential for errors caused by data transmission. Finally, the fully integrated LIMS allows lab management to analyse all laboratory data within a single platform and ensures that all necessary data is available to relevant stakeholders at any time.
Pharmaceutical manufacturers must ‘prioritise end-to-end informatics investments and align metrics for innovation, domain expertise, operational efficiencies and quality
In a recent report, entitled Product Innovation Requires Laboratory Informatics Systems to Transcend Phases (9/26/13), Gartner analyst Michael Shanler noted that today’s laboratory informatics systems ‘are, for the most part, disconnected.’ He insisted that pharmaceutical manufacturers must ‘prioritise end-to-end informatics investments and align metrics for innovation, domain expertise, operational efficiencies and quality.’ The key word here is end-to-end: in laboratory informatics, the whole system must be more than the sum of its parts. The value of each component of the informatics system – the LES, SDMS and LIMS – increases as the parts become more tightly integrated.
Too often, laboratories consider a LIMS as a standalone investment that does nothing but define workflows and manage samples. When labs adds more capabilities such as an ELN or an SDMS to handle other lab functions, they often fail to fully integrate them into their existing LIMS. This is a mistake – integration should be a top priority for lab administrators, and this is one of the most important steps a lab can take to effectively manage complexity, ensure product quality, simplify training and streamline compliance processes. This is true whether the lab is sited in a single location or part of a geographically dispersed operation.
Today, a lab’s informatics system is more integral than ever to a manufacturer’s overall quality, reputation and profitability. Without a highly integrated and entirely paperless informatics system in place, the lab cannot play this role. With it, however, the lab is a strategic asset to the company and one of its drivers for sustainable growth in a rapidly changing industry.
