Jim Stommen , Contributing Writer06.11.12
Two parts of the medical product manufacturing process that the users of those products probably don’t give much thought to are, in the end, among the most important.
Sterilization and packaging are getting more attention than ever before, impacted both by closer regulatory scrutiny of the entire supply chain and by the pervasive “faster, better, cheaper” mantra that drives the operations of medical device manufacturers these days.
Industry experts representing various segments of the process talked with Medical Product Outsourcing about some of the developments that are impacting both the sterilization and packaging aspects of the manufacturing process.
John Kowalski, Ph.D., principal consultant with Sterigenics International Inc.’s SteriPro Consulting unit, said the proverbial “next big thing” for the sector isn’t some whiz-bang new sterilization technology, but rather a possible change in philosophy.
“The biggest thing coming down the road for the sector,” he said, is a re-examination of whether what he called “the historically accepted sterility assurance level of 10-6” is really required for medical products. The 10-6 value was an arbitrary number; to protect patients, you might not require it. So if sterility assurance levels were to come up to say, 10-4, which is being discussed, then that allows for lower radiation dose, a milder treatment, so there is some synergy there.
“It’s clear that device developers would like to use lower radiation doses and make products with lower bioburden and thereby be able to justify and validate a lower sterilization dose,” Kowalski said.
“People are saying that if we don’t have to drive the sterility assurance level to such a low value, that would open the door for products that are difficult to sterilize because they’re so sensitive to sterilization processes, particularly radiation.”
Chris Ramsden, CEO of Fall River, Mass.-based Millstone Medical Outsourcing, said that in order to ensure a successful packaging process, a multi-functional team has to be involved from the start.
“You can’t have sales, marketing and finance driving this,” Ramsden said. “You have to have manufacturing process engineers, packaging engineers, sterilization experts. If you’re really looking at keeping the total cost of delivery of this product or product family down, you have to get everybody in the room up-front.
“The failures that we have seen are when sales or marketing and finance make decisions that override some of the functional experts, trying to save pennies or dimes in a design, picking pouch over tray or not going with an additional foam or support, say, and then you end up failing the validation or a real-time aging test,” he said. “It is penny wise but pound foolish if you don’t listen to those functional experts. When they are not listened to, you can almost predict failure.”
Asked a similar question about where packaging and sterilization considerations fit into the overall process, Tish Anger, vice president of regulatory and quality assurance at Southmedic Inc., a Barrie, Ontario-based manufacturer and distributor of operating room products, said, “Something we really stress to our customers is that your packaging requirements need to be discussed at the design stage of a project. That may seem like a logical comment, but all too often the packaging is an afterthought.”
Maurice (Moe) Lavimodiere, manufacturing concepts and sales manager at Southmedic, put it succinctly: “It’s amazing how still today, in 2012, some companies think, ‘Well, we’ll just put it in a pouch and seal it and then we’re done, right?’ And we have to come back with, ‘No, that’s not it.’”
Tom Stephan, executive vice president of sterilization services provider Synergy Health AST LLC, based in San Diego, Calif., said that cost reduction pressures on medical device manufacturers “continue to focus on all facets of packaging—smaller, cheaper primary packages, cost-effective shelf cartons, low-cost corrugated shipper cases, more cases per pallet and more efficient logistics.
Packaging drives cost effectiveness from manufacturing, sterilization, distribution, logistics and ultimately waste. The common goal is to get more devices per unit volume and less packaging mass per device unit.”
Stephan noted that packaging optimization and change can impact sterilization parameters.
“Generally, the denser the product, the more difficult and costly it is to sterilize,” he said. “With changes in packaging, validations must be performed, adding cost and lead time to the process.”
Jim Carnall, vice president and chief operating officer of Command Medical Products Inc. in Ormond Beach, Fla., a contract manufacturer of single-use disposable medical devices, characterized packaging as part of the process, just like assembly.
“We always have to understand what it is that the customer wants and then work with them to try to figure out what is the best way to establish the best materials and process to handle that,” he said.
“Additional considerations for us involve what facility we are going to be using to package the product and what type of sterilization method is required for the device. We also need to keep in mind if the packaging we are developing is an intermediate step used to sterilize and/or transport work in process or subassemblies to our customers for further processing or if it is going to be shipped to distribution and end users. It all depends on what our customer is going to do with it once they get it.”
The Push for “Milder” Processes
Sterigenics’ Kowalski said of the role of sterilization: “The current sense is that everyone needs more specialized, customized processes that are milder on products. With all the new drug/device combinations, you need to minimize the effects on the product while achieving sterility, so using processes that are adjusted—or ‘tuned up’ is the term I use—to make sure the product attributes survive and also attain the required sterility assurance level is more and more important now.”
He said everybody wants just-in-time manufacturing, but people really need to be “in tune” with design for sterilization versus sterilization being a consequence at the end.
“The worst thing that can happen is to make a medical product and at the end you find you can’t EtO (ethylene oxide) it, you can’t irradiate it and you find you’re into some kind of aseptic processing,” he said. “That’s really the most important message out there, for people to design for sterilization.
Ultimately that gets you to faster, better, cheaper because that gets you to an end that is predictable.
You have to pay up-front and pay attention to design for sterilization so that when you get to the end, you know it’s going to work vs. hitting the wall on something and getting what I call ‘late bad news.’ You really need to design for sterilization—that gets you faster, better, cheaper because there are some things you can’t change late in the product development process. All that upfront work pays off in the end.”
Kowalski said that another matter of considerable impact is that there are “so many new, small start-up companies with some magic molecule or device, and those people know everything about their device, molecule, or chemistry, but they lack knowledge about packaging and/or sterilization, so they have to get those folks engaged early to help them through that part of the process.”
Asked about the impact of scrutiny by the U.S. Food and Drug Administration (FDA) and other regulatory bodies on how sterilization is being carried out today, he said he sees regulators getting increasingly tough on reviewing sterilization validation activities.
“You really have to get that done right,” Kowalski said. “And the other key issue is that you follow the relevant national/international standards. Making sure that you’re aligned with the international standards is what the Notified Bodies and FDA are going to be paying attention to.”
Kowalski lauded the FDA for responding positively to moves to push broader acceptance of international standards.
“The agency has a web page listing for the ISO standards that they have accepted, most of which they have accepted in their entirety,” he added. “They’re really in the game on that.”
Business Pressures Bring Tighter Focus
“This year, the whole orthopedic industry that we deal with on the implant side is seeing a tremendous amount of financial pressure, so they’re looking for speed and cost savings and shorter lead times,” Millstone Medical’s Ramsden said. “Programs are moving more quickly now; there’s not the luxury of being able to stretch these things out. There’s a lot of pressure now on these big organizations—people are very focused.”
In terms of “the next big thing,” he said there are a “bunch of things” that people are trying in order to
cut total costs of delivery.
“One thing we’re seeing is the continued movement from non-sterile to sterile in trauma and spine; a lot more trauma and spine products are being sterile-packed,” he said. “And companies continue to move toward disposable instruments as another trend—it’s not new, but it continues to build momentum. Sterile packaging of disposable instruments allows hospitals to be more efficient during surgery and helps to reduce the risk of infection. Many of our customers are working on ways to package instruments and implants that are patient- and surgery-specific. The goal is to maximize disposable instruments while using the least amount of packaging.”
He said another key point is that the company continues to encounter more porous coatings and new coatings for implants, which Ramsden characterized as “a game-changer” for packaging.
Ramsden noted that with new materials like biological coatings becoming part of new medical products, “there are a whole bunch of different requirements depending on the coatings. The coatings can be extremely abrasive, so any movement within a packaging configuration will produce damage to the inner layer of the packaging or also create residue, almost like a particulate. So, it’s no longer looking at, say, a titanium hip—it’s like handling a titanium hip that’s covered in sandpaper. A lot of customers have thought they could use existing packaging designs with these new coatings, and it has proven not to be true.”
He added: “Some of these abrasive coatings, even during the manufacturing process, when we see them come to us, are somewhat akin to handling Velcro. They pick up every fiber and hold onto it, so you have to be very careful in every aspect of the manufacturing process as to what you’re exposing these implants to, because they do hold onto debris and fiber extremely well.”
Asked the most important element in packaging—the design, the materials or the process—Ramsden has no doubt: “The design. That defines the materials and the process in my mind. We have some really innovative people and have seen some incredibly innovative designs recently to save space, to minimize the amount of foam or buffer material. People are getting a lot more creative on the design side of packaging, especially on tray design. Those innovations have enabled people to package product that has what I’ll call difficult characteristics safely and reliably. So, I think it’s really design, followed by determining process and materials.”
He said the FDA’s focus on management of the supply chain in recent years clearly has been heard within the device industry.
“They certainly made their point, and medical device manufacturers or big ortho are still responding to that. We have several customers who are going through what I’ll call a packaging vendor rationalization. There have been so many recalls that they’re taking a very close look at the number of vendors they have packaging for them and rather than having every manufacturer package that device, they’re cutting down on the number of vendors that they’re actually going to let package their products.”
Education Plays a Big Role
Anger said that one of the most important aspects of Southmedic’s relationships with its client companies is in proving education in areas where it has particular expertise.
“Because we often deal with smaller companies that don’t necessarily have their own regulatory department, and they may lack expertise in sterilization and packaging,” she said, “we try to provide guidance and education to our customers and look at the options that are available to our customers based on our experience.”
She added: “When we look at design considerations and sterilization end-points, we need to look at sterilization and obviously productivity, but the packaging has to be right up there in your design input, and that’s up to industry to continue to educate their customers when we’re doing contract manufacturing.”
One of the hidden challenges in packaging, she said, is the cost, noting that the cost of the validations can add up quickly.
“Even if you have a really good validation master plan, and you educate your customer on the requirements and mitigating those risks, validation of both the equipment and the process is a requirement,” she said. “I think that’s an area that really can be an unknown because validation can explode, depending on the complexity, the automation, the technology involved.”
Lavimodiere said another thing that many customers don’t realize is that engineering changes “start validation all over again.”
Anger elaborated on that point.
“Now that we’re entering this field of more automation and validated equipment, with every change you make to that process, you have to look at validation impact,” she said. “The regulators expect you to have due diligence on understanding what impact you have on your processes by making those changes.”
Unfortunately, according to Anger, this tends to slow processes down and can impact speed to market and launch time.
“But in the long run, you end up mitigating your risks and mitigating significant costs that could be incurred through those risks,” she said.
With new materials such as biological coatings becoming increasingly common among new medical products, Anger noted that their impact on sterilization and packaging requirements can be considerable.
“We manufacture a premium scalpel blade that has a polymer coating, and when we were looking at validating those processes, we acquired a company and took on the technology, but then had to really start from the ground up in developing and validating a sterilization process for the product,” she said.
After looking at several existing methods that were rejected for technical reasons, Southmedic ended up developing a new dry heat sterilization process.
“It’s interesting because dry heat is such a rare form of sterilization these days; not a lot of companies do it,” she said. “That’s one example of not only looking at the product and the coating, which prevented us from going our usual route, but then there was the packaging, which prevented us from going our alternative route.”
When asked about whether any of the three main elements in packaging—the design, the materials or the process—is more important than the others, Anger said: “My first thought is that they’re equally important, but without a good design and an understanding of the appropriate materials, and a repeatable process, the company’s liability would be very high. Repeatability in your process is a difficult thing to predict unless you’re looking at your design up front and your appropriate materials during your design phase. Especially for sterilized products, because you have to look at compatibility with different sterilization processes, not just for the product but for the packaging as well.”
Packaging a Focus for Cost-Cutting
Stephan of Synergy Health said sterilization must continue to be focused on the evolution of medical devices that perform a function as well as therapeutic outcome. Biologically derived products such as collagens and tissues, and bioabsorbable products require tight tolerance sterilization parameters to ensure predictable performance and expected medical outcomes.
As for the next big thing, he cited custom cycles in EtO, which “focus on lower exposure temperatures to protect thermo-labile materials used in emerging medical device products.” Noting that these “exotic” cycles often relate to small volumes of very expensive products, Stephan said that necessitates “changing supplier selection decisions to those based on flexibility and capability... away from the traditional high-volume throughput economy-of-scale model.”
He cited his company’s move to X-ray radiation sterilization, saying that products may be sterilized on pallets, thus avoiding labor cost and potential product-handling damage or mixing.
“X-ray radiation sterilization has the capability to maintain tight dose tolerances in pallet orientation with the process flexibility and routine turn-times normally associated with electron beam,” Stephan said.
He said that as the last two steps in the manufacturing process, packaging and sterilization usually are the last to be considered in the design phase. But in his view, “early design incorporating polymers and packaging with known compatibility to the sterilization processes is a must.”
Stephan used the example of gas-impermeable packaging, or moisture barriers designed to extend the functional life of devices, which often can create obstacles for sterilization methods.
“Let’s not lose sight of the fact that sterilization is a volume-driven business,” he added. “Smaller boxes with more units often translates to less cost per device, but making them too small or too densely packed can reverse the cost equation. There is no standard rule, so companies need to work closely with their sterilization vendor to drive optimization.”
Asked whether there are hidden challenges in sterilization and packaging, he said that packaging/polymer formulations can have a “subtle yet severe” impact on performance after sterilization.
“These formulation changes could result in color changes, odors, shift in peel strength, sterilant residuals, and more,” he said. “This has led to very stringent no-change agreements with packaging and sterilization vendors that lock down formulations and processing parameters.”
As for the FDA’s closer scrutiny of the entire supply chain, he said that scrutiny is the result of system failures.
“The delicate balance is between innovation and validation. The concern or perception of increased regulatory scrutiny has slowed the change process and in many cases stifled it,” he said.
Understanding Needs is Paramount
Carnall said that from Command Medical’s perspective, “Packaging and sterilization always have been important, and we continue to work with our customers to understand their requirements and the validations required for our clients and our organization internally, etc., to make sure we meet those requirements.”
On the sterilization side, he said gamma and EtO seem to go back and forth as far as which one is the preferred option.
“It really is dictated by our customers and the new contracts we are awarded,” he said. “The most recent rumblings have revolved around the potential for E-beam sterilization as an alternative to gamma. This option is particularly attractive, as it has often been seen as cost-effective and more precise than gamma and we have an E-beam sterilization facility in close proximity to our Nicaragua manufacturing facility.”
Carnall added: “As a contract manufacturer, most of the time the sterilization method has already been determined by the time the product has been brought to us, so it is not often that we have the opportunity to sway the direction of the sterilization method.”
He said that packaging considerations depend on the customer.
“A lot of times they’ll say, ‘Okay, come up with a packaging scheme,’” he explained. “In order to do this, we have to really understand what the intended use is and what they’re going to do with it once we package the device.”
The biggest challenge is making sure that the packaging meets the needs of whatever the customer’s process is going to be so as not to adversely affect their process, according to Carnall.
“There are two or three key things that you’re trying to accomplish,” he said. “The first is that you have to make sure that the packaging allows for complete sterilization. Second and third—and you can debate the order—are cost and time.”
Jim Stommen, retired editor of industry publication Medical Device Daily, is a freelance writer focusing on the medical product sector.
Sterilization and packaging are getting more attention than ever before, impacted both by closer regulatory scrutiny of the entire supply chain and by the pervasive “faster, better, cheaper” mantra that drives the operations of medical device manufacturers these days.
Industry experts representing various segments of the process talked with Medical Product Outsourcing about some of the developments that are impacting both the sterilization and packaging aspects of the manufacturing process.
John Kowalski, Ph.D., principal consultant with Sterigenics International Inc.’s SteriPro Consulting unit, said the proverbial “next big thing” for the sector isn’t some whiz-bang new sterilization technology, but rather a possible change in philosophy.
“The biggest thing coming down the road for the sector,” he said, is a re-examination of whether what he called “the historically accepted sterility assurance level of 10-6” is really required for medical products. The 10-6 value was an arbitrary number; to protect patients, you might not require it. So if sterility assurance levels were to come up to say, 10-4, which is being discussed, then that allows for lower radiation dose, a milder treatment, so there is some synergy there.
|
A Millstone Medical Outsourcing professional programs a heat sealer used in packaging. Photo courtesy of Millstone Medical Outsourcing. |
“People are saying that if we don’t have to drive the sterility assurance level to such a low value, that would open the door for products that are difficult to sterilize because they’re so sensitive to sterilization processes, particularly radiation.”
Chris Ramsden, CEO of Fall River, Mass.-based Millstone Medical Outsourcing, said that in order to ensure a successful packaging process, a multi-functional team has to be involved from the start.
“You can’t have sales, marketing and finance driving this,” Ramsden said. “You have to have manufacturing process engineers, packaging engineers, sterilization experts. If you’re really looking at keeping the total cost of delivery of this product or product family down, you have to get everybody in the room up-front.
“The failures that we have seen are when sales or marketing and finance make decisions that override some of the functional experts, trying to save pennies or dimes in a design, picking pouch over tray or not going with an additional foam or support, say, and then you end up failing the validation or a real-time aging test,” he said. “It is penny wise but pound foolish if you don’t listen to those functional experts. When they are not listened to, you can almost predict failure.”
Asked a similar question about where packaging and sterilization considerations fit into the overall process, Tish Anger, vice president of regulatory and quality assurance at Southmedic Inc., a Barrie, Ontario-based manufacturer and distributor of operating room products, said, “Something we really stress to our customers is that your packaging requirements need to be discussed at the design stage of a project. That may seem like a logical comment, but all too often the packaging is an afterthought.”
Maurice (Moe) Lavimodiere, manufacturing concepts and sales manager at Southmedic, put it succinctly: “It’s amazing how still today, in 2012, some companies think, ‘Well, we’ll just put it in a pouch and seal it and then we’re done, right?’ And we have to come back with, ‘No, that’s not it.’”
Tom Stephan, executive vice president of sterilization services provider Synergy Health AST LLC, based in San Diego, Calif., said that cost reduction pressures on medical device manufacturers “continue to focus on all facets of packaging—smaller, cheaper primary packages, cost-effective shelf cartons, low-cost corrugated shipper cases, more cases per pallet and more efficient logistics.
Packaging drives cost effectiveness from manufacturing, sterilization, distribution, logistics and ultimately waste. The common goal is to get more devices per unit volume and less packaging mass per device unit.”
Stephan noted that packaging optimization and change can impact sterilization parameters.
“Generally, the denser the product, the more difficult and costly it is to sterilize,” he said. “With changes in packaging, validations must be performed, adding cost and lead time to the process.”
Jim Carnall, vice president and chief operating officer of Command Medical Products Inc. in Ormond Beach, Fla., a contract manufacturer of single-use disposable medical devices, characterized packaging as part of the process, just like assembly.
“We always have to understand what it is that the customer wants and then work with them to try to figure out what is the best way to establish the best materials and process to handle that,” he said.
“Additional considerations for us involve what facility we are going to be using to package the product and what type of sterilization method is required for the device. We also need to keep in mind if the packaging we are developing is an intermediate step used to sterilize and/or transport work in process or subassemblies to our customers for further processing or if it is going to be shipped to distribution and end users. It all depends on what our customer is going to do with it once they get it.”
The Push for “Milder” Processes
Sterigenics’ Kowalski said of the role of sterilization: “The current sense is that everyone needs more specialized, customized processes that are milder on products. With all the new drug/device combinations, you need to minimize the effects on the product while achieving sterility, so using processes that are adjusted—or ‘tuned up’ is the term I use—to make sure the product attributes survive and also attain the required sterility assurance level is more and more important now.”
He said everybody wants just-in-time manufacturing, but people really need to be “in tune” with design for sterilization versus sterilization being a consequence at the end.
“The worst thing that can happen is to make a medical product and at the end you find you can’t EtO (ethylene oxide) it, you can’t irradiate it and you find you’re into some kind of aseptic processing,” he said. “That’s really the most important message out there, for people to design for sterilization.
Ultimately that gets you to faster, better, cheaper because that gets you to an end that is predictable.
You have to pay up-front and pay attention to design for sterilization so that when you get to the end, you know it’s going to work vs. hitting the wall on something and getting what I call ‘late bad news.’ You really need to design for sterilization—that gets you faster, better, cheaper because there are some things you can’t change late in the product development process. All that upfront work pays off in the end.”
Kowalski said that another matter of considerable impact is that there are “so many new, small start-up companies with some magic molecule or device, and those people know everything about their device, molecule, or chemistry, but they lack knowledge about packaging and/or sterilization, so they have to get those folks engaged early to help them through that part of the process.”
Asked about the impact of scrutiny by the U.S. Food and Drug Administration (FDA) and other regulatory bodies on how sterilization is being carried out today, he said he sees regulators getting increasingly tough on reviewing sterilization validation activities.
“You really have to get that done right,” Kowalski said. “And the other key issue is that you follow the relevant national/international standards. Making sure that you’re aligned with the international standards is what the Notified Bodies and FDA are going to be paying attention to.”
Kowalski lauded the FDA for responding positively to moves to push broader acceptance of international standards.
“The agency has a web page listing for the ISO standards that they have accepted, most of which they have accepted in their entirety,” he added. “They’re really in the game on that.”
Business Pressures Bring Tighter Focus
“This year, the whole orthopedic industry that we deal with on the implant side is seeing a tremendous amount of financial pressure, so they’re looking for speed and cost savings and shorter lead times,” Millstone Medical’s Ramsden said. “Programs are moving more quickly now; there’s not the luxury of being able to stretch these things out. There’s a lot of pressure now on these big organizations—people are very focused.”
In terms of “the next big thing,” he said there are a “bunch of things” that people are trying in order to
cut total costs of delivery.
“One thing we’re seeing is the continued movement from non-sterile to sterile in trauma and spine; a lot more trauma and spine products are being sterile-packed,” he said. “And companies continue to move toward disposable instruments as another trend—it’s not new, but it continues to build momentum. Sterile packaging of disposable instruments allows hospitals to be more efficient during surgery and helps to reduce the risk of infection. Many of our customers are working on ways to package instruments and implants that are patient- and surgery-specific. The goal is to maximize disposable instruments while using the least amount of packaging.”
He said another key point is that the company continues to encounter more porous coatings and new coatings for implants, which Ramsden characterized as “a game-changer” for packaging.
Ramsden noted that with new materials like biological coatings becoming part of new medical products, “there are a whole bunch of different requirements depending on the coatings. The coatings can be extremely abrasive, so any movement within a packaging configuration will produce damage to the inner layer of the packaging or also create residue, almost like a particulate. So, it’s no longer looking at, say, a titanium hip—it’s like handling a titanium hip that’s covered in sandpaper. A lot of customers have thought they could use existing packaging designs with these new coatings, and it has proven not to be true.”
He added: “Some of these abrasive coatings, even during the manufacturing process, when we see them come to us, are somewhat akin to handling Velcro. They pick up every fiber and hold onto it, so you have to be very careful in every aspect of the manufacturing process as to what you’re exposing these implants to, because they do hold onto debris and fiber extremely well.”
|
The conveyor system at Synergy Health’s electron beam service center in Saxonburg, Pa. Photo courtesy of Synergy Health. |
He said the FDA’s focus on management of the supply chain in recent years clearly has been heard within the device industry.
“They certainly made their point, and medical device manufacturers or big ortho are still responding to that. We have several customers who are going through what I’ll call a packaging vendor rationalization. There have been so many recalls that they’re taking a very close look at the number of vendors they have packaging for them and rather than having every manufacturer package that device, they’re cutting down on the number of vendors that they’re actually going to let package their products.”
Education Plays a Big Role
Anger said that one of the most important aspects of Southmedic’s relationships with its client companies is in proving education in areas where it has particular expertise.
“Because we often deal with smaller companies that don’t necessarily have their own regulatory department, and they may lack expertise in sterilization and packaging,” she said, “we try to provide guidance and education to our customers and look at the options that are available to our customers based on our experience.”
She added: “When we look at design considerations and sterilization end-points, we need to look at sterilization and obviously productivity, but the packaging has to be right up there in your design input, and that’s up to industry to continue to educate their customers when we’re doing contract manufacturing.”
One of the hidden challenges in packaging, she said, is the cost, noting that the cost of the validations can add up quickly.
“Even if you have a really good validation master plan, and you educate your customer on the requirements and mitigating those risks, validation of both the equipment and the process is a requirement,” she said. “I think that’s an area that really can be an unknown because validation can explode, depending on the complexity, the automation, the technology involved.”
Lavimodiere said another thing that many customers don’t realize is that engineering changes “start validation all over again.”
Anger elaborated on that point.
“Now that we’re entering this field of more automation and validated equipment, with every change you make to that process, you have to look at validation impact,” she said. “The regulators expect you to have due diligence on understanding what impact you have on your processes by making those changes.”
Unfortunately, according to Anger, this tends to slow processes down and can impact speed to market and launch time.
“But in the long run, you end up mitigating your risks and mitigating significant costs that could be incurred through those risks,” she said.
With new materials such as biological coatings becoming increasingly common among new medical products, Anger noted that their impact on sterilization and packaging requirements can be considerable.
“We manufacture a premium scalpel blade that has a polymer coating, and when we were looking at validating those processes, we acquired a company and took on the technology, but then had to really start from the ground up in developing and validating a sterilization process for the product,” she said.
After looking at several existing methods that were rejected for technical reasons, Southmedic ended up developing a new dry heat sterilization process.
“It’s interesting because dry heat is such a rare form of sterilization these days; not a lot of companies do it,” she said. “That’s one example of not only looking at the product and the coating, which prevented us from going our usual route, but then there was the packaging, which prevented us from going our alternative route.”
When asked about whether any of the three main elements in packaging—the design, the materials or the process—is more important than the others, Anger said: “My first thought is that they’re equally important, but without a good design and an understanding of the appropriate materials, and a repeatable process, the company’s liability would be very high. Repeatability in your process is a difficult thing to predict unless you’re looking at your design up front and your appropriate materials during your design phase. Especially for sterilized products, because you have to look at compatibility with different sterilization processes, not just for the product but for the packaging as well.”
Packaging a Focus for Cost-Cutting
Stephan of Synergy Health said sterilization must continue to be focused on the evolution of medical devices that perform a function as well as therapeutic outcome. Biologically derived products such as collagens and tissues, and bioabsorbable products require tight tolerance sterilization parameters to ensure predictable performance and expected medical outcomes.
As for the next big thing, he cited custom cycles in EtO, which “focus on lower exposure temperatures to protect thermo-labile materials used in emerging medical device products.” Noting that these “exotic” cycles often relate to small volumes of very expensive products, Stephan said that necessitates “changing supplier selection decisions to those based on flexibility and capability... away from the traditional high-volume throughput economy-of-scale model.”
He cited his company’s move to X-ray radiation sterilization, saying that products may be sterilized on pallets, thus avoiding labor cost and potential product-handling damage or mixing.
“X-ray radiation sterilization has the capability to maintain tight dose tolerances in pallet orientation with the process flexibility and routine turn-times normally associated with electron beam,” Stephan said.
He said that as the last two steps in the manufacturing process, packaging and sterilization usually are the last to be considered in the design phase. But in his view, “early design incorporating polymers and packaging with known compatibility to the sterilization processes is a must.”
Stephan used the example of gas-impermeable packaging, or moisture barriers designed to extend the functional life of devices, which often can create obstacles for sterilization methods.
“Let’s not lose sight of the fact that sterilization is a volume-driven business,” he added. “Smaller boxes with more units often translates to less cost per device, but making them too small or too densely packed can reverse the cost equation. There is no standard rule, so companies need to work closely with their sterilization vendor to drive optimization.”
Asked whether there are hidden challenges in sterilization and packaging, he said that packaging/polymer formulations can have a “subtle yet severe” impact on performance after sterilization.
“These formulation changes could result in color changes, odors, shift in peel strength, sterilant residuals, and more,” he said. “This has led to very stringent no-change agreements with packaging and sterilization vendors that lock down formulations and processing parameters.”
As for the FDA’s closer scrutiny of the entire supply chain, he said that scrutiny is the result of system failures.
“The delicate balance is between innovation and validation. The concern or perception of increased regulatory scrutiny has slowed the change process and in many cases stifled it,” he said.
Understanding Needs is Paramount
Carnall said that from Command Medical’s perspective, “Packaging and sterilization always have been important, and we continue to work with our customers to understand their requirements and the validations required for our clients and our organization internally, etc., to make sure we meet those requirements.”
On the sterilization side, he said gamma and EtO seem to go back and forth as far as which one is the preferred option.
“It really is dictated by our customers and the new contracts we are awarded,” he said. “The most recent rumblings have revolved around the potential for E-beam sterilization as an alternative to gamma. This option is particularly attractive, as it has often been seen as cost-effective and more precise than gamma and we have an E-beam sterilization facility in close proximity to our Nicaragua manufacturing facility.”
Carnall added: “As a contract manufacturer, most of the time the sterilization method has already been determined by the time the product has been brought to us, so it is not often that we have the opportunity to sway the direction of the sterilization method.”
He said that packaging considerations depend on the customer.
“A lot of times they’ll say, ‘Okay, come up with a packaging scheme,’” he explained. “In order to do this, we have to really understand what the intended use is and what they’re going to do with it once we package the device.”
The biggest challenge is making sure that the packaging meets the needs of whatever the customer’s process is going to be so as not to adversely affect their process, according to Carnall.
“There are two or three key things that you’re trying to accomplish,” he said. “The first is that you have to make sure that the packaging allows for complete sterilization. Second and third—and you can debate the order—are cost and time.”
Jim Stommen, retired editor of industry publication Medical Device Daily, is a freelance writer focusing on the medical product sector.
