Partnership key to challenges of testing, regulation
CUYAHOGA FALLS, Ohio—From the suppliers of raw materials that forge the medical device, to those who test the device, to the drug manufacturers who fill the device and those who package and help deliver the life-saving pharmaceuticals, patient safety is the top priority.
And that only can be accomplished through the perhaps overused but no less important notion of partnership. How do all of these spaces work together to meet the very basic human requirements of health and safety?
A panel of experts in these fields discussed these essential goals and related challenges as part of Rubber & Plastics News' 2021 Healthcare Elastomers Conference, during a May 4 virtual talk on "Regulatory Testing in Elastomers."
Panelists included Alex Kakad, global product manager with Tekni-Plex Medical Inc. of Wayne, Pa.; Ana Barbur, vice president of chemical analytical services with the Akron Rubber Development Laboratory Inc. in Akron; and Gael Peron, vice president of medical device testing with Smithers, also of Akron.
"Regulations are changing extremely fast, as is the role here in testing labs," Barbur said. "Some customers are more comfortable with the changes, but a number of them are lost as far as what can be used and what is available to be used. I feel an increased need to be up to speed to know the compounds to be able to guide customers through these requirements.
"We need to work together to manage these expectations."
Technology is indeed changing at a rapid rate, opening new and innovative ideas in health care. But this can be a double-edged sword for both the medical device and medical elastomer testing companies and manufacturers, as regulatory bodies typically lag behind the development of new devices in implementing new certifications and regulatory thresholds.
Open-source hardware is available, and personal and single-use medical devices are becoming more prevalent.
Peron noted that the industry is witnessing an industrial revolution of sorts, with all elements evolving.
"Regulatory agencies are really focusing on people using proper techniques, using the correct requirements with medical devices—and people are becoming much more educated about that, bringing more challenging techniques. This is the essential interaction between the biological side and the understanding of these interactions—the circle continues."
Kakad called it a "sea change in the bio-processing market."
"Things continue to advance," he said. "Especially for critical application areas, such as pumping and sensitive drug transfer. We are seeing a new generation of chemotherapy drugs coming on the market with less of a threshold for preservative loss.
"There also are cell and gene therapies and the need for products to be suspended in DMSO (dimethyl sulfoxide). The challenge as a component manufacturer is keeping up with innovations in therapeutic areas."
The interaction of the medical device container and what it contains is at the forefront for Peron and Smithers, namely the leachables and extractables that can infiltrate the drug from the device and packaging, and vice versa.
And with an evolving regulatory landscape, the ability to provide information to assist clients can be a challenge.
"The overall knowledge base is increasing, evolving toward sterilization of the techniques used to test products," Peron said. "There are always two sets of innovators—the suppliers that can keep building more complex, multi-material products and the end users.
"Never underestimate the innovation of end users or the idea of using a product in a way that is not necessarily the primary intent of the product. This challenges the system. It goes back to patient safety—the entire testing chain is built to ensure patient safety."
Barbur and ARDL, one of the world's major hubs for chemotherapy device delivery testing, often advise customers on steps moving forward with their device.
"We have seen major changes of new updates and changes to devices," she said of the regulatory landscape. "It is important to know and define correctly what is leaching and extracting (within the devices and drugs)."
But the devil can be in the details, Kakad added.
"It's not as easy looking at particulate testing and particulate count. You have to work very closely in understanding downstream risk," he said. "Is there a risk of an embolism from larger particles in the bloodstream? Is it a flow characteristic issue? It is not a one-size-fits-all model."
Pandemic causes market pressure
Certainly the impact of the coronavirus pandemic and related supply line challenges cannot be ignored as these crucial issues are addressed, and the panelists agreed that the pressure placed on raw material suppliers and downstream manufacturers can be overwhelming.
Like the market turbulence of 2017-18, TPE, LSR and HCR pricing and capacity have become volatile once again, in major part due to the coronavirus pandemic. Testing agencies and manufacturers had to rethink their priorities and drug device manufacturing companies had to retool in their production.
"Drug manufacturers were put under a lot of pressure, whether in the production of vials or other components," Kakad said. "Elective surgeries went down substantially or stopped altogether as ventilators and other PPE became more important. Quality assurance testing became more important. Certain resins were not available due to the uptick in ventilators and other PPE due to the pandemic."
And just as the pandemic required manufacturers to respond rapidly to these changes, capacity issues reached testing companies as well.
"For every valve manufactured, there is a stopper that is mated to that valve," Peron said. "By my count, the market at one point was between 16 billion and 18 billion vials strong—this puts immense pressure on supply chain and capacity. From a societal perspective, prioritizing the testing of PPE was the right thing to do.
"But these types of supply chain issues will take time to resolve. Suppliers have to reroute toward specific applications or specific segments. Fortunately, we understood this and we were able to rapidly adapt and get them through (testing)."
ARDL, which did comprehensive testing for customers on nitrile and blended nitrile gloves and PPE gowns, also was forced to adapt to the rapid-fire changes in the market.
"There were just extraordinary requirements for everything—new compounds, failures on PPE and how to fix them," Barbur said. "However big we thought the wave was going to be, it was so much bigger than that. As manufacturers tried to stockpile, they had no idea how much they needed to stockpile. We have seen new blends for applications that we were not used to seeing.
"But the market reacted to this extraordinary demand, and as a testing lab we had to react to those changes. Many options had to be screened at one time. There was no time, and testing was needed immediately."
In some elastomer spaces, critical capacity shortages remain even as the world's largest economies emerge from the pandemic. As such, the single-supplier philosophy has been brought into question.
"Is the one-supplier philosophy still practical? It depends on the supplier and on the components required," Kakad said. "It is hard to have multiple sources for each product. Auditing these things takes time, effort and adds to cost. You try to look at the components that have the most (drug) product contact.
"And there are other questions—do you have global supply capabilities and redundant facilities? Vertical integration allows for better control through to the final product, but all of this is a case-by-case basis. For those who use a single supplier, it is paramount that the supplier has good control over its raw materials."
Barbur said ARDL has seen a desire from its customers to have a second supplier for raw materials, "certainly more than several years ago," and Peron noted that ultimately all parties involved have to make the "make or buy" decision.
"Some performed product testing in-house while others did so externally. It is always a case of is there someone better equipped than me to do this? Is it cost-competitive? The answer will evolve with time," he said.
Looking to the future
The world of research and development in medical device elastomers is perhaps the most rapidly changing environment of any in the world, with the stresses of low capacity and the strains of a pandemic driving innovation.
But new technology is in the DNA of the medical elastomer field, regardless of outward pressures.
"The most exciting thing is that we are bringing together multiple innovations from multiple industries," Peron said. "We have patients using drug delivery devices in their homes rather than going to a doctor's office. From a material perspective, the more we know about their potential, the better. With coatings, for instance, that is still an area that has many more years of innovation to occur."
Barbur noted that medical devices will transition from 3D printing to 4D printing and beyond, and those technical leaps will require testing for safety.
"The trend right now in laboratories are the many new compounds we are seeing," she said.
Kakad said cell therapies and insulin delivery devices require DMSO processing, and such solvent materials will become more prevalent in the medical market.
"For some, like the COVID-19 vaccines, minus-80-degree Celsius storage is required," he said. "Manufacturers were losing their product to cracking as they came back up to (ambient) temperatures. So lower temperatures across the board will be needed."
And regulatory bodies like the FDA are getting much more specific in their requirements (if not quicker in their announcements of those requirements).
"To be honest, some of these changes are welcome," Barbur said. "Most of these changes are welcome, in my opinion."
Outside of the governmental regulatory bodies, trade organizations are beginning to set their own guidelines for product testing thresholds, Kakad said.
"Beyond governing bodies, this will be a trend as well, establishing testing standards for uniform material comparison," he said.
But Peron disagreed, saying that testing companies sometimes are left in the dark, which can be frustrating for customers.
"What we are seeing is a continuous wish to push the limit of detection," he said. "There is definitely an unsatisfaction with seeing 'unknown,' 'unknown,' 'unknown' next to the results. Trying all the time to push for more and more understanding as to what is behind those limits, this goes back to risk assessment."
Kakad reiterated that collaboration across companies and industries is key.
"In testing and working with suppliers, one of the terms that is overused is 'partnering.' But this is exactly what is important in what you're trying to accomplish—forming a risk mitigation plan that is more robust.
"There will be more challenges and more opportunities ahead."
Peron agreed that it is rewarding to know that "we are all in this together."
"The ultimate benefit is the societal benefit—not looking at the transactional relationship, but looking at things as development partners," he said.