Making The Switch To Single-Use: Have You Thought Of Everything?
By Trisha Gladd, Editor, Life Science Connect
In 2014, Prolong Pharmaceuticals followed through on their decision to build a facility for the scale-up of their lead product, SANGUINATE. With over 20 years of experience overseeing manufacturing teams at some of pharma’s biggest names, including Shire and Genzyme, Chuck Hart, Prolong’s director of manufacturing, knew this would be no simple task.
Beyond the sheer magnitude of the project, the new facility is not going to manufacture SANGUINATE utilizing the process used at small scale by Prolong. This is essentially multi-use open containers with reusable tangential flow filtration (TFF) membranes. Instead, the Prolong team made the decisions necessary to switch the process to one that is primarily closed, fully-automated, and uses single-use technology (SUT) almost exclusively. This also meant moving away from the traditional SIP and CIP stainless steel equipment.
Because of the lessons Hart has learned working with and designing single-use equipment at other facilities, he knew there were many important factors Prolong would need to keep in mind during the facility design and equipment selection process. He recently sat down with me to discuss some areas he feels are sometimes overlooked when switching from traditional stainless steel to SUT.
In the first article of two-part series, Hart touches on several considerations to keep in mind when it comes to both equipment design and vendor relationships.
Design Should Be A Fit For Both The Equipment And Its Users
If you’ve reached the point in the process where you’re sitting down to create the design for your facility, then you’ve most likely already done an analysis to determine if SUT is right for you. Regardless of a desire to increase flexibility or lower cost (or both), the deciding factor in stainless vs. SUT is tank capacity. As of right now, the highest commercial scale SUT bioreactor in the industry is 2,000 liters (though Hart believes there is additional testing and design work in process to increase to 3000L or even 5000L). “If a company has a high yield, low volume process or a continuous perfusion process that could consistently draw off of a bioreactor, then 2,000 liters is probably sufficient enough,” explains Hart. “However, for a fed batch reactor, you need to focus on volume. Stainless steel bioreactors that I have been involved with had upwards of 20,000 liter capacity. At that volume, stainless steel would likely be the right choice.”
While SUT equipment typically carries a smaller footprint than stainless steel, that does not mean you won’t completely save on space. With disposables, the storage space required gets much larger. This is because, in addition to housing raw materials, you also have to store everything you would use as a disposable. At Shire, Hart says the storage space was not just a separate room; for SUT, the company built and designed the warehouse to one that was approximately twice the size of any he had ever seen. Space, he says, that was not wasted.
Finally, it’s a guarantee as well as a necessity for various areas of expertise to be involved in the design of an SUT facility. Prolong’s existing team responsible for the design and construction of their new facility currently has nine members from a company of about 70 employees. However, he has also worked with much larger groups at companies that employ thousands. Regardless of how many experts you have at your disposal, a valuable lesson he learned is to get the user involved early. “As people begin to design bags, equipment, components, etc., one area where they can fail is only using the engineering team to come up with the design,” says Hart. “Engineers do not typically get into the logistics of the systems set-up, so they don’t have to worry about the details of system integrity, such as bag or tubing set defects or issues with bag setup. You need someone from the manufacturing team who is going to be on the floor handling the equipment every day and can help determine if the design is feasible.”
Help Wanted: Trusted Vendors Only
As SUT adoption increases, the vendor pool is ripening. Companies like Sartorius and Pall have become well-known suppliers of single-use equipment, but there are also new companies beginning to dip their toes into the waters of this budding area of opportunity. In both cases, regardless of experience, the vendor should be able to validate the effectiveness of their equipment and its performance claims. They can do this by providing information from existing customers (even if they don’t want to divulge the name), such as if the customer using it has been commercially approved and/or if they’re using it regularly. Having a history is very important.
This may not be possible with new technologies or new companies, but Hart says they should at least have test data they can share. “Everybody’s trying to be the next company that comes up with the newest ideas and that’s great,” he says. ”But the vendor needs to be able to provide a great deal of valid data that shows the equipment can perform at the level it’s specified to.”
By not ensuring this, you could potentially end up with unsuitable equipment and wasted dollars. The vendor chosen needs to be aware of the impact something like that could have on an overall plan. In one situation at a previous company, Hart recounted a vendor contract that stated any time there was a vendor failure on a bag, it would cost the supplier $10K. At the time, it appeared to be an appropriate failure cost, until you consider how much a leak in a bag could cost the customer, which could be millions. “Obviously, no vendor is going to pay the millions lost, but the cost to them should be a feasible percentage of what that failure means as it applies to your profit,” he says. “With stainless steel equipment, the vendor sells you a piece of equipment that you have to test in the field. Once it’s qualified, you are responsible for preventative maintenance, but in the grand scheme of things, the vendor did what they were supposed to do. With single-use equipment, a new bag is essentially a new buffer or process tank every time. The vendor has to understand what a high failure rate of those bags could mean.”
Another key component after appropriate vendor selection is to ensure that the vendor/customer partnership is carried through the life of the single-use component. Having that two-way communicative partnership with your SUT vendor goes a long way in keeping the vested interest high by both parties.
Hart also urges companies to establish a second source vendor or, as he likes to call them, an “alternate source” vendor. This is because he would rather not establish a primary vendor until he is absolutely confident that the vendor understands what they need to do. “An alternate source vendor gives you continuity, and it allows you to change on the fly,” he explains. “If something happens to your primary vendor and you don’t have that alternate source, you are in trouble.” He adds that you should also let your primary vendor know there is an alternate source. This open and honest relationship prevents surprises down the road and keeps competition alive.
Finally, regardless of whether the company is experienced or is new to the market, your salesperson should not come off as someone who is just trying to get items off the shelf. They should be an expert in their product who can answer questions and give you confidence that they are going to be able to provide the help or expertise you need with their product when you need it.
In the next article, Hart discusses an area that some feel could be SUT’s biggest weakness and that is bag dependability. He covers topics, such as proper fitting of bags, handling, as well extractables and leachables.