Transforming molecular LDT workflow with the Roche FLOW Solution

The Regional Virus Laboratory (RVL), located at Belfast’s Royal Hospitals Complex, is the only UKAS-accredited provider of clinical virology testing services for hospitals, GPs and public health professionals in Northern Ireland. Serving a population of 1.8 million and around 1600 users, the RVL offers a broad range of conventional serology, antigen detection and molecular tests for the diagnosis of viral, bacterial and other infections. Since 2014, the RVL Molecular Section has used the Roche FLOW Solution for the molecular analysis of a wide range of infectious diseases. The laboratory offers a complex portfolio of around 40 laboratory developed tests (LDT) PCR assays, both qualitative and quantitative, that target viral and bacterial DNA or RNA—preparing their own master mixes and using universal PCR amplification conditions.

The RVL analyses an increasing number of specimens every year (figure 1). Dr. Susan Feeney, Clinical Scientist in the RVL Molecular Section, comments:

“We have experienced significant growth in our workload in recent years. For example, looking at influenza test requests alone, numbers never really recovered following the H1N1v pandemic in 2009 and, by 2013, the number of influenza specimens we received annually had superseded the 2009 peak (figure 2).”

“Before FLOW was installed, our expanding workload, combined with continuing demand for faster turnaround times, was placing enormous pressure on service delivery,” Dr. Feeney recalls. “Added to this, we had the normal seasonal pressures, the need to develop assays for new and re-emerging pathogens, and a changing staff mix, due to the retirement of several experienced members of staff who were replaced by less experienced junior grades.”

Working under such pressure, the delivery of a safe, efficient and timely service was an enormous challenge to the molecular team and so they examined their workflow to identify risks and possible solutions.

“Our main concerns were patient safety, staff safety, clerical errors and reporting,” Dr. Feeney explains. “The risks for each of these issues were mainly related to the manual handling of samples and manual transcription or input of data. It became clear to us that our most pressing needs were additional automation and improved interfacing between systems.”

When members of the RVL Molecular team saw a presentation about the Roche FLOW Solution at a Roche user meeting in Dublin, they could see its potential to solve their automation and interfacing needs.

“Our previous workflow placed an enormous burden on staff, with many laborious manual tasks (figure 3),” Dr. Feeney says. “There was a risk of repetitive strain from copious pipetting, huge pressure to enter data correctly and several bottlenecks, particularly in the reporting of results, which had to be printed, matched to the daily worksheet and then manually entered into LIMS.”

“After hearing about FLOW, we realised that we already had most of the basic elements for a FLOW Classic line (figure 4)— primary sample handling instrument, a MagNA Pure 96 System for sample extraction and a LightCycler^® 480 System. All we needed was another liquid handling system for PCR setup and for FLOW to enable them all to communicate, with each other and with LIMS.”

Implementation of the Roche FLOW Solution began in the summer of 2014 with the installation of the PCR Setup instrument and FLOW software. Then the assay protocols were entered into the system and tested prior to FLOW going live in September 2014 (figure 5).

Introduction of assays to the FLOW Solution was staggered, starting with a few simple, single target assays. Then the gastrointestinal panels were added, followed by quantitative and multiplex assays and biopsies. By the end of 2014, all assays had been added to FLOW apart from the respiratory and cerebrospinal fluid (CSF) panels.

“Compared to our previous workflow, since all the systems are now interfaced and communicate with each other, the FLOW workflow eliminates the time-consuming manual tasks (figure 3) and reduces the associated risks of repetitive strain injury, transcription errors, and result delays due to bottlenecks,” Dr. Feeney comments.

“FLOW is a safe, completely closed, barcode-controlled solution that allows specimens, controls, master mixes and reagents to be traced easily, and provides a valuable audit trail.”

Passing their first UKAS inspection in June 2015, the molecular team moved forward with their plans to install a second FLOW line and to introduce the remaining test panels. Dr. Feeney continues:

“We decided to install a second FLOW line for our respiratory specimens. Not only would this increase our capacity, but it would also provide a valuable backup system.”

“The FLOW Flex Solution made sense to us, allowing us to have two FLOW lines in a cost and space efficient solution, requiring just one additional MagNA Pure 96 System since each line would have a single liquid handling instrument for both primary sample handling and PCR Setup (figure 6). We installed the second FLOW line in February 2016 and by June 2016 we were running all our assays on FLOW, including all specimen types: bloods, urines, swabs, CSF and biopsies - everything that we need to test.”

“Previously, we would run a worksheet at a particular time in the morning, after which further samples received that day would not be processed until the following day,” Dr. Feeney explains. “Now we perform four runs every day, two on each FLOW line, and there is no need to batch or delay samples. This has improved our efficiency and turnaround times, allowing us to achieve our improvement promise of results in no longer than 48h.”

Since the RVL Molecular Section transferred all of their LDTs to FLOW, they have experienced a very different working environment. Dr. Feeney describes the change:

“With our two FLOW lines, we have improved efficiency, increased our capacity and reduced manual hands-on time. This solution has removed reporting bottlenecks and massively reduced our paper trail. Overall, it has created a much safer, calmer working environment.”

“We recently experienced the highest ever number of positive flu samples in a week (1512), but looking around the laboratory, you would never have known we were at such high capacity. Everything was so organized and calm—completely different to when we experienced workload peaks previously, even with lower-skilled staff.”

“Much of our confidence comes from the first class support we have received from Roche,” she continues. “In the beginning, when we were getting used to the system, our calls were answered immediately and any issues were resolved within the day. We would provide input about our needs and found that these were addressed in subsequent software updates. We really felt heard and that our feedback was valued.”

The transformed working environment was praised in the laboratory’s 2016 UKAS inspection. Commenting on the reorganisation of work processes within the Molecular Section, with two FLOW Solution lines now in place, the UKAS report stated, “this has improved service provision overall” and “it is commendable the improvement there has been in this area”. The report goes on to say that “efficiency overall is impressive” and that “it is noticeable that the atmosphere is calm, stress-free and conducive to the production of accurate results.”

“Faster turnaround times and confidence in our results allows us to offer an improved service to our end users,” Dr. Feeney concludes, “and helps us to achieve our primary goal of delivering a safe and efficient service.”