By Ed Miseta, Chief Editor, Clinical Leader
Follow Me On Twitter @EdClinical
With the number of biologics now in development and soon to be making their way into clinical trials, the preservation of cells, tissues, and organs are suddenly increasing in importance. Mike Rice, CEO of BioLife Solutions, believes companies handling the manufacturing, storage, and transportation of these materials need to be focused on improving the yield and extending the shelf life of these time and temperature sensitive biologics as they get moved from one location to another.
“Today, we have clinical trials involving living cells and tissues,” says Rice. “If you're producing and shipping pills to wholesalers and pharmacies, the process is not too complicated. Pills and non-biologic medicines are not temperature sensitive and they have a long shelf life. That is not the case with cell therapies and human organs and tissues. In that space, everything being shipped is time and temperature sensitive.”
One example Rice cites is the apheresis process. With this process, blood is removed from the body and components such as plasma, platelets, or white blood cells are removed. The remaining blood is returned to the body. The portion containing T-cells is sent to a lab or drug manufacturing facility where they are genetically engineered to recognize an antigen on targeted tumor cells. The T-cells are expanded in a lab, sent to the location where the patient is being treated, and infused into the patient to guard against recurrence. The yield and shelf life of the engineered T-cell product during this process are critical for potential commercial distribution and reimbursement.
“Best practices of biopreservation mandate the use of complimentary tools to meet challenges presented in cold chain distribution of time- and temperature-sensitive biologics,” states Rice. “That means the right media in which to bathe these cells and tissues so they can withstand the stress of hypothermic storage, freezing, and recovery. Extending the shelf life is also important, as there has to be enough time available for those companies with a worldwide geographic distribution. Companies no longer want to raise hundreds of millions of dollars to build a plant on every continent because of a product’s shelf life. That model no longer works.”
New Science Requires New Solutions
Today, new shipping container solutions on the market feature electronics and integrated thermal couples. These features allow the devices to transmit data to a cloud app, allowing for trace and surveillance capabilities by pharma clients who can intervene if something goes wrong. The devices also measure the true temperature of the payload and monitor whether the package is subjected to shock, vibration, and humidity.
The market is certainly driving the need for these solutions. Going forward there will be a growing appreciation for real-time surveillance of time- and temperature-sensitive biologics. There are a lot of reasons for this. One factor Rice cites is his belief that regulators are going to demand it now that the technology is available and viable.
“Cell therapy companies will soon have to prove, through auditable documentation, that a payload was maintained within its temperature range throughout the transit process and was administered within its shelf life,” notes Rice. “If they don’t, I can see the day coming when they will no longer get paid, or their customers won't get paid. That is a serious situation that I think will wake up the industry.”
If regulators begin to make these demands, pharma will be faced with requirements very different from today’s current practices, which can still involve putting cells in some type of foam cooler with ice packs. Oftentimes there is no temperature monitoring performed. When there is, it takes the form of a data logger that records but does not transmit information. The devices are not integrated, they are not sitting next to the payload, and they do not measure the true temperature of the payload.
“There are some biologics that might be able to withstand a broader temperature range,” adds Rice. “However, in the cell therapy space, you have product that needs to be shipped at temperatures ranging from two to eight degrees Celsius. The temperature cannot vary outside that range. For sponsors, the real challenge revolves around liability. These cell shipments are sensitive and can be damaged if subjected to the stresses of improper biopreservation.”
Errors Can Add Up
Rice likes to use an aviation example to illustrate what can go wrong in the shipping process. Often, when the FAA discovers the root cause of a catastrophic plane crash, it's typically not one error that occurs. There are a series of cascading errors that build upon one-another. In the cell therapy space, he believes errors occur because current practice entails performing some type of validation and then making assumptions.
“If cells being used in a clinical trial have to travel from point A to point B, a data logger is used in three sample shipments. If the data show no temperature issues occurred, an assumption is made that this will always be the case. That’s a ridiculous assumption, because temperature fluctuations can and do occur. Incredibly, in many cases, no one even reviews the data logger to see if any fluctuations occurred. When they do, it can occur weeks after the patient has been infused. Then there is the additional problem of cells arriving dead and no one performing an assay on them before they are infused. The whole set-up is a recipe for disaster because if an early-stage clinical trial fails, the company running the trial may not even know why it failed. Did the cells not do what they were supposed to or were the cells already dead when they were infused? Dead cells are never going to cure cancer.”
Not Just For Oncology
Although new shipping devices are obvious for immunoncology trials, they are a fit for every clinical indication using cell therapies. While about half of the current cell therapy clinical trials are targeting blood cancers and solid tumors, cells are now being used to treat age-related macular degeneration, diabetes, stroke, HIV, multiple sclerosis, movement disorders, and more. Many believe that in our lifetime the use of cells and tissues will become a significant spend in relation to the current investment we make for drugs and devices. “This is a significant opportunity and things are lining up for what I believe will be an exciting time for patients and an interesting and perhaps crazy time for investors,” says Rice.
For many companies, the biggest logistical challenge going forward will be an under appreciation for just how challenged some of the current cold chain technologies and practices really are. That current thinking will create both clinical and economic risks for companies. Without solutions that have proven performance and real-time monitoring, clinicians will be flying blind.
“One of the analogies I like to use comes from the organ transplant space,” says Rice. “When an organ arrives, the transplant surgeon has to determine if they will use it. They will feel it and palpate it. They will determine if it is firm and examine its color. That's crazy, and it simply is not good enough. Consider that a lot of oncology patients are late stage. Many are simply too sick to endure another apheresis collection to make a new batch of cells. There are many reasons for the industry to properly ship and preserve samples, and we have to start with the human ones. My challenge now is convincing the industry we have to do better.”