Personalized Testing - BioReliance Builds a Biologics Clearance Service Facility That’s a Home Away from Home
Let's face it - travelling for business reasons is not very glamorous. Beyond the inevitable snafus of just getting to your destination, there are always worries of technology glitches and concerns of staying in touch with the home office to deal with.
In the highly specialized, yet fundamentally important, biological testing services segment of the pharmaceutical contract services industry, the deficiencies of business travel can be magnified by the length of time spent on-site monitoring testing procedures, and the lack of a dedicated space to call your office away from home.
BioReliance, a company that provides testing and manufacturing services to pharmaceutical and biopharmaceutical companies, realized that the absence of full featured and fully customizable biological clearance testing facilities was an opportunity. The company’s recently opened testing facility in Rockville, MD offers their clients private and secure work lounges along with fully modular lab spaces that can be designed, equipped and ready-to-go upon their arrival.
HISTORY AND BACKGROUND
Bioreliance has been providing services to the pharmaceutical industry since 1947. First, with the production of serum for cell cultures and tissues and commercial supply of cell cultures and reagents. In 1955 the company created the first biosafety product for polio vaccines and also developed safety testing for the first rocks brought back from the moon.
In 2012 BioReliance was acquired by Sigma-Aldrich Corporation in order to provide their customers with a single-point provider whose services would span the entire drug discovery, development and commercialization spectrum. As part of the SAFC business unit, BioReliance provides cost-effective contract services, offering more than 1,000 tests or services related to biologics safety testing, specialized toxicology and animal health services. BioReliance also offers contract manufacturing services for gene therapy and vaccine products.
For the past 25 years, the company’s expertise has been focused on the safety testing of products made via biomanufacturing processes. About 80% of its revenue derives from the testing of biological (“large molecule”) products for human use according to regulatory specifications. Testing of these products is important because unlike small molecule drugs made by chemical synthesis, there are inevitably variations between batches in biomanufacturing processes; additionally, there is potential for contamination by human pathogens. The remaining 20% of the business’s activities are focused on small molecule product testing, and animal specimen testing.
CLEARANCE SERVICES – EXPLAINED
In basic terms, clearance services involve replicating a purification or separation process on a small scale, spiking the material to be purified with a virus and then observing how well the process removes the virus.
It’s a very specific type of service and one which not many service providers offer.
According to Kathy Martin Remington, Ph.D., BioReliance’s Principal Scientist, Development Services/PD & Clearance Biologics Testing, who works very closely with clients to design their studies, these studies are done to verify that manufacturing can remove a contaminating virus. If one were present.
She continues, in more detail, “Clients come to our site – send their scientists – they will perform a small-scale version of their manufacturing process step.”
“We spike it with virus – help them in any way and assay the virus to determine how much clearance is afforded. We can actually help perform the process for them. It’s a little different than other testing services and the client is very involved. A lot of time they will be here for a few weeks working in our labs doing their study.”
She details a typical study, “We look at their manufacturing process – usually a purification process – starting say with a fermentor harvest and the client wants to get rid of impurities. They want to purify their products and refine the steps they use so they will focus on several key process steps. The client will send us the process intermediate they want tested just before a step in the process, for example the chromatography process. We would add virus to the material that goes in to the chromatography column, send the material through the chromatography step, and take the material that comes off the chromtoagrapgy columns and see how much virus is cleared from that step.”
This is a very important test as regulators expect that there are certain steps in the process that include virus removal and inactivation.
As mentioned, this is a very specific type of service and one that requires specialized skills and dedicated facilities. Therefore it is not one that many companies have the in-house resources to perform. Clearance services requires a large amount of cell culture and virology capabilities and most companies do contract out their studies. In fact BioReliance does studies for most of the large biopharma companies.
But, according to Ailsa Shepherd, M.Phil., Senior Director, Lab Operations, Biologics Testing, clearance services are just one part of a safety strategy.
“The other part is screening for potential contaminant,” she says. ”The difference here is that we are mimicking an artificial contamination event – we are adding an artificial virus in the beginning of a unit process operation at the lab-scale – and based on what we’ve put in and what we get out we can determine how safe the step is. It’s very different from the typical screening assays that are done further downstream.”
“When you perform the screening assays you don’t want to detect virus,” adds Remington. “If you do you toss it away. For the clearance part - we are actually adding a lot of virus to it – this is kind of a back-up capacity - if the screening should fail or if we didn’t detect it in the screening assay– then we have the capacity in the manufacturing capacity to add an extra layer of protection.”
Working with such large quantities of viruses is a key reason so many companies hire someone else to do this type of testing as Shepherd points out, “That’s one of the key reasons why most companies will contract out this work because we are working with such high levels of virus – most companies would have to have a separate facility from their manufacturing facility to work with these high levels of virus. This is one of the main reasons it’s not done in house - fear of contamination.”
The work here is being done at a small scale” says Shepherd, “not at the manufacturing scale. The critical parameters have to be mimicked in this setting – so for most of them its temperature, protein concentration, the chromatography steps. For inactivation steps you are really looking at a group of experimental parameters that can be mimicked through temperature control, pH control, etc. That’s easy to do on a small scale.”
Remington concludes, “Each manufacturer is expected, when they submit their biological safety data, that the work they did on the small scale actually matches the large scale.”
INSIDE THE CLEARANCE SERVICES FACILITY
BioReliance’s new facility was built and equipped using client and user feedback. The goal was to make the client’s experience be as user-friendly, easy and as smooth as possible; because many times these clients are on-site for a week or more depending on the type of study.
With this in mind, BioReliance created a facility that features fully equipped study lounges that clients can call their own. Each lounge is equipped with a comprehensive set-up to allow for remote monitoring of their tests in the nearby lab areas, plus the lounges allow them to keep in contact with their home offices.
“You can imagine they are being plucked out of their own work environment and they still have things to take care of at their home office – so if they are on a conference call or doing computer work – this room allows them to still be in touch with the lab,” says Shepherd.
Pedro Diaz, BioReliance’s Lab Manager, describes the technology offered on each lounge. “In each lounge there are smart – touch screen panels – so clients can view what’s happening in the labs as their tests are being performed.”
He continues, ”There are three parts of this technology – camera mode, presentation mode and smart technology which actually allows them to see into the lab. Camera mode allows clients to see into the space, they can zoom in to see particular dials or gauges in real time. This gives them the flexibility to leave the lab and still interact with people in the lab.”
“In presentation view – clients can view computer screens from the lab in the lounge. We have two systems set up – for example, if four tests are running they can view all four processes at the same time in the lounge. Users can zoom in on the results as well. This is a real-time view of the lab technician’s view.”
The team at BioReliance reports that this set-up has been positively received by their clients. Clients are happy to find a space that is entirely dedicated to them – and – in regards to security and protection of intellectual property – all test results can’t be seen by the BioReliance team and just as importantly, any other users of the clearance facility.
Since testing requirements vary from client to client, the lab areas had to be as flexible as possible and were built around a modular footprint to give 100% functionality of the space.
Shepherd explains, “Being able to tailor the lab to the client depending on the equipment they need and the number of people they have is an important advantage of this facility. This space has been designed to allow us to do that.”
“We are very conscious of giving a total solution to the client and enhancing the client experience especially in this service offering area. That’s what it’s all about. It’s all about the client experience.”
“We have the capability to have a lot of equipment and a lot of people in our labs space – or if it’s a small study – and a client doesn’t want a lot of clutter – it can be set up that way,” says Shepherd.
Diaz adds, ”Since it’s not their facility we want the client to have as much input as possible to make the space feel like their space. The number of people and equipment can be tailored before they arrive.”
In order to make each lab as functional and flexible as possible – each lab features electrical panels in the ceiling so equipment can be set up in the center of the room affording 360 degrees access to all equipment.
All data is captured and stored in the lab and can be backed up for safe storage. Computers and all other equipment are backed-up by UPS systems or generators.
Diaz explains how everything in the lab is monitored. “Equipment is also monitored – if there is an occurrence or event – we can see what happened, incubators, freezers, etc. are all monitored for their individual parameters.”
Returning to the modularity of the labs, Diaz emphasizes the flexibility of the labs. “Everything can be moved out and brought back in – the labs are completely modular and customizable.”
Equipment is easily moved in on carts – if a client brings their own equipment – it can be brought on site – and used.
“We want clients to see this as a modular approach,” says Diaz. “To set up their lab as if it were their own lab. When they walk in the door – they will already know where to put the equipment.”
The completion of the Rockville, MD facility finishes BioReliance's upgrades to its global offerings, having also renovated and expanded their Stirling, Scotland facilities in 2011.
"It's all about simplifying the viral clearance process," says Archie Cullen, president of BioReliance. "Any time a client comes to us, they are assured that their study is expertly designed and performed by personnel that have participated in thousands of successful studies."