The drive for connected labs in pharmaceutical QA/QC

Few QA/QC labs still cling to the old paper-based notebook systems of the past, but there’s far more to becoming a paperless lab than simply eschewing paper.

The paperless lab has been discussed for the past 15-20 years but it is finally happening, and nowhere is this more evident than inside quality assurance/quality control (QA/QC) laboratories.

To be successful in eschewing paper, labs must adopt a smart infrastructure that drives quality, not only in the lab, but throughout the organisation. An integrated informatics solution is the engine that drives quality product release and a culture of continual process improvement.

However, Gartner analyst Michael Shanler has observed that currently many labs “are, for the most part, disconnected”.

In his recent report, ‘Product innovation requires laboratory informatics systems to transcend phases’, Shanler recommended that manufacturers “prioritise end-to-end informatics investments and align metrics for innovation, domain expertise, operational efficiencies and quality”.

The move to a more connected laboratory is driven by both the productivity drivers Shanler describes and significant technology improvements.

Quality by design

In 2004, the FDA introduced Quality by Design (QbD) in ‘Pharmaceutical cGMPs for the 21st Century - A Risk-Based Approach’. While this concept is not new to many industries, this was the first attempt to apply these principles to the pharmaceutical industry. QbD is built on the concept that well-understood products and processes are more efficient and produce higher quality products resulting in less product non-conformance. The FDA’s goal was to improve pharmaceutical companies’ productivity, to ensure patient safety and to prevent drug shortages in the marketplace. The quote below, pulled from a 2012 FDA presentation on the pharmaceutical quality system, makes this point succinctly:

“We rely upon the manufacturing controls and standards to ensure that time and time again, lot after lot, year after year the same clinical profile will be delivered because the product will be the same in its quality… We have to think of the primary customers as people consuming that medicine and we have to think of the statute and what we are guaranteeing in there, that the drug will continue to be safe and effective and perform as described in the label.” (Janet Woodcock, MD)

Uncompromising quality is essential to any pharmaceutical company. Informatics plays a critical role in ensuring that organisations realise the improved product quality and operational efficiency that adherence to QbD principles provides.

Today’s informatics infrastructure

QA/QC laboratories need a tightly controlled process and well-managed laboratory to drive predictive analytics and to prevent substandard products before they occur. An end-to-end informatics solution warns the organisation before non-conformances occur by monitoring critical product attributes creating a proactive versus reactive environment. Laboratories address these needs through the use of several systems: Lab Execution Systems (LES), Scientific Data Management Systems (SMDS) and Laboratory Information Management Systems (LIMS).

LES has become a critical component of today’s paperless lab ensuring that quality processes are followed in the laboratory and that the methods built on QbD principles are followed in day-to-day laboratory operations. LES drives users through any laboratory procedure in a stepwise fashion. This provides technicians with the direction they need to execute processes safely, and in a consistent manner. It also assures laboratory management that good laboratory practices are used and that SOPs are being followed by experienced and newly trained laboratory personnel. Maintaining a consistent approach to activities like sample preparation, instrument calibration and maintenance, and analytical testing is critical to a good scientific process. Lab managers can then be certain that all of their results are a true assessment of final product quality.

An SDMS lets you integrate instruments across the lab and centralise data capture, allowing for long-term data archiving but, more importantly, data visualisation from the archive — all accessed from the LIMS. An SDMS archives the original raw data files from the instrument along with a normalised representation in XML, without the need to restore the data to the original instrument workstation or install the instrument software on every computer. The real scientific data and the results gleaned from it are a critical part of QbD. The final product specification is determined by comparing the analytical results to determine which formulation and process parameters yield the best product.

As part of a paperless lab environment, an SDMS integrated with the LIMS reduces paperwork, manual review time and data transcription, which improves efficiency, productivity, consistency and quality while reducing costs dramatically. SDMS also provides secure access to archived files for as long as necessary and enables more efficient and defensible reporting to regulatory authorities.

LIMS remains a critical part of any pharmaceutical manufacturing organisation’s infrastructure. Today’s LIMS goes far beyond just the management of samples, tests and results. It also provides resource management, allowing organisations to forecast fewer sample volume and resource needs. It provides dashboard views that allow organisations to see how their lab is operating and identify any data that is trending towards warning or failure limits. These lab management activities are essential, but organisations also need to be able to drive the day-to-day operations of the laboratory as well.

Having a smart infrastructure built on a state-of-the-art informatics solution at its core enables another critical benefit in the lab — automation. Even smart instruments must undergo regular performance verification. And how often this is done depends on many factors, including the frequency of use. Because instrument failure — or having a system go out of specification — can negatively impact quality, production or compliance down the road, any risk is unacceptable. A LIMS can save considerable time helping labs adhere to precise rules and requirements, automating critical procedures on predefined schedules.

When all systems are aligned, the convergence of people, processes and technology is transformative. Problems arise when these systems aren’t fully integrated and these disparate systems become out of sync. At a macro level, breakdowns occur at three key points: data capture, data transcription and data management. Put another way, the key to an efficient lab that delivers uncompromising quality is having smart instruments within a smart infrastructure. This starts with SOPs for highly standardised methods and processes, which are handled by the LES, and includes raw instrument data generated by the analytical instruments used in those experiments, all of which is handled capably by the SDMS.

What lab managers really want is a truly connected system that provides lab management, drives lab operations and integrates all of the data-generating sources, and ties all that data together in one centralised location. A modern LIMS needs to be a complete informatics infrastructure by providing a LIMS, SDMS and LES in one.

Achieving much-anticipated integration

Today’s paperless lab can more aptly be called an integrated lab. The trinity of LIMS/LES/SDMS enables lab managers to achieve full instrument integration, manage their methods and workflows, retrieve and archive any kind of raw laboratory data and export those results across the organisation to ERP systems, for example — all in whatever format is required by recipients.

The ability to manage the entire process in a tightly integrated solution, one that functions as a single piece of software, dramatically streamlines laboratory operations while minimising the cost of ownership, implementation, validation and ongoing maintenance.

An example of this is Thermo Fisher Scientific’s SampleManager LIMS, which includes built-in functionality for LIMS, LES and SDMS as well as integration technologies. What’s more, when labs plan for such seamless integration it enables lab managers to codify a ‘do it right every time’ process approach, which is in alignment with QbD processes, providing the transparency necessary to identify and remove non-value-add steps, while lowering the cost of training new staff. With LES functionality available as part of a LIMS implementation, SOPs and methods are automatically established electronically so that for any lab personnel, new or seasoned, the LIMS acts as their workflow, manual and constant guide.

It’s easy to see the LIMS, LES, SDMS ‘stack’ as a lab-centric view of pharmaceutical business, but that would be a mistake. The ability to run efficient labs and protect the brand by safeguarding product quality are both enterprise-level concerns. As such, the LIMS needs to be fully integrated with ERP systems: in fact, many work requests coming into QA/QC laboratories are actually initiated in a manufacturer’s ERP system, which for many companies is the bridge between its manufacturing execution system (MES) and other systems such as the LIMS.

Conclusion

In many organisations, a LIMS is a standalone investment, managing workflow and sample testing and generating appropriate reports. If the lab needs additional software, such as an ELN or SDMS, those systems are then implemented and sometimes, but not always, integrated with the LIMS so that lab operations are more streamlined and data is easier to manage.

In a QA/QC lab, however, a LIMS such as SampleManager that is pre-built with LES and SDMS functionality delivers end-to-end workflow and data capture that is literally designed for quality. The benefits of having all these capabilities resident in a single system are myriad, starting with lower total cost of ownership, ease of training and administration, streamlined compliance and better overall quality control. And all of this is possible across vast geographies or contractual partnerships, all of which can be managed holistically.

Organisations that haven’t done so already need to make this year a major inflection point for laboratory technology, especially within the QA/QC function. After all, the evidence is stacking up that the costs of inaction clearly outweigh the investment that is required for change.