Packaging and sterilization are two very important steps in the medical device manufacturing process. Although they are relatively inexpensive components of the overall process of getting a product to market, they are two of the most critical. Failure by either results in delays, higher costs, questions about reliability in the minds of end users and possibly serious health complications to the patient.
"The goal for all devices is to have a package that protects the device and allows it to be effectively sterilized, that stays intact during transit and storage so the product remains safe and sterile until used, yet is also easy to open and remove the product at the point of use," said Betty Howard, gamma tech team manager for STERIS Isomedix Services in Morton Grove, Ill., a provider of contract irradiation (gamma or electron beam) and ethylene oxide sterilization services.
Like other industries, orthopedic manufacturers are trying to reduce costs as much as possible. The biggest challenge is finding the most cost-effective methods of packaging that will not compromise high levels of quality. Companies are looking for ways to use less packaging wherever possible to reduce waste, make handling easier, reduce storage and shipping space and lower costs. Products must still pass regulatory requirements, such as ship testing, accelerated and real-time aging, sterilization validations and sealing validations. "It's also becoming more costly to meet FDA requirements," said Kelly Lucenti, president of Millstone Medical Outsourcing in Fall River, Mass., a provider of validation engineering, advanced inspection and sterile and non-sterile packaging. "OEMs are becoming more conservative in their decision-making as the FDA becomes more stringent in enforcement."
The packaging and sterilization teams for most orthopedic manufacturers, as well as their vendors and outsourcing partners, are working together at the design stage to create a smooth, streamlined packaging and sterilization process that prevents last-minute problems from arising. To keep costs down, companies continuously are looking for packaging materials and designs that will reduce cycle times and improve throughput, while still maintaining the integrity of the orthopedic product.
Key Trends in the Industry
Outsourcing partners have reported a trend by OEMs toward more customized packaging. "Manufacturers are trying to come up with multiple options for different hospital set-ups," indicated Brenda Sparks, director of corporate accounts for Centurion Sterilization Services, a contract packaging, kitting, sterilization and laboratory-testing firm in Michigan. "However, what works at one hospital may be completely inappropriate for another. Manufacturers are seeking input from the end user so we can work together to provide a better package that ultimately assists the end user."
Another trend in sterilization is the movement away from excessive sterilization treatments.
"For ethylene oxide (EtO) sterilization, this means the optimization of cycles instead of automatically using traditional overkill cycles," said Trabue D. Bryans, vice president and general manager of WuXi AppTec in Marietta, Ga., a laboratory and manufacturing outsourcing company. "For radiation sterilization, this means using lower sterilization doses that correlate to the product bioburden, rather than choosing a historic dose such as 25 kGy."
Bryans also noted that, for both sterilization and packaging, more companies are grouping products into families, which is a more effective way of achieving compliance while reducing costs, both in initial validations and maintenance of the validations.
The pressure from OEMs to lower the cost of packaging systems yet still improve efficiencies within the medical device supply chain, including sterilization, seems to increase on a yearly basis. "For
A Millstone Medical Outsourcing professional vacuum packages a femoral stem in an inner nylon pouch. Photo courtesy of Millstone Medical Outsourcing.
example, some orthopedic companies are striving to change EtO sterilization cycles to an 'all in one' cycle to reduce cycle throughput and costs," said Jane Severin, director of technology for Oliver Tolas, a manufacturer of sterile-grade medical device packaging and pharmaceutical packaging in Grand Rapids, Mich. "To do this, their packaging must be designed to be resistant to sterilizer creep. Also all-in-one cycles add physical stress on the seals."
Vendors also have noted an increased interest in high-barrier flexible packaging, such as foil to foil or foil to film pouches, especially for combination devices that also deliver drugs. More OEMs are using foil pouches because they can use a vacuum pull to remove oxygen, along with a nitrogen flush and bar seal.
"Foil pouches can be gamma-sterilized, which is preferable to EtO because there is no wait for outgassing," said Lucenti. "Our goal is to have the percentage of oxygen remaining to be under 1 percent. For some customers we can achieve less than 0.2 percent oxygen in the pouch. The benefit is better preservation of materials because materials degrade more slowly over time when less oxygen is present. After the vacuum pull, nitrogen flush, and bar seal, the pouches can be sent for gamma sterilization, and OEMs don't have to wait for the outgassing required with EtO sterilization."
Removing the oxygen to such low levels does require special equipment, such as nitrogen flush pouch sealers. The low results can be tricky to achieve and is an art and skill acquired from significant experience with different products, pouch sizes, procedures and testing.
Packaging and Sterilization Challenges
Medical device manufacturers are sensitive to the fact that the package must be durable enough to prevent damage of an expensive medical device and be able to withstand the effects of sterilization, without degradation of the package. End users in a hospital setting also like to see the product through a clear rigid package before opening it.
Product and package design inputs include a number of key attributes that must be considered when designing a package or selecting a sterilization method. "Some of these are product material, product configuration and weight, package material, primary package closure method (seal) and strength, label type and method of print, product surface area, package surface area, package porosity, package design, secondary and tertiary package materials, designs, and density, product protection requirements (UV, oxygen, water vapor), desired shelf life and transport modes," said Severin.
Two major parts of the process are the selected materials (polymer, metal, etc.) and the physical characteristics (size, weight, sharp edges, etc.) of the device. "For example, an OEM wanted us to package an instrument with jagged edges in a pouch because it would be less expensive and faster to get to market," said Lucenti. "We advised against it, but they were concerned about cost and decided to take the risk. The instrument failed ship testing because it poked holes in the pouch. The result was a failed product launch, and the OEM had to begin the whole packaging and sterilization process from the beginning."
Companies also are shifting toward using a more standard size and gauge of PETG (an easily recycled polymer) for their packages, which allows them to order the PETG in larger quantities to save money, versus ordering several different sizes at an increased price.
"With increased environmental awareness in the supply chain by both OEMs and end users, more companies are interested in using PETG," said Mark Schmitt, account manager at Pacur, an extruder of medical-grade materials located in Oshkosh, Wis. "PETG is a FDA-approved co-polyester that also uses the '1' recycling code. Polyesters are the most recycled polymers-this is an added advantage for PETG from a 'green' perspective, because other polymers are not as environmentally friendly."
Bulky, heavy, projectile-shaped implants are definitely a challenge for maintaining the integrity of thesterile barrier system throughout the entire distribution environment, including sterilization.
"As far as the testing that is required for sterilization validation, large orthopedic implants are more difficult because they typically must be tested intact, and in many cases do not fit into traditional test containers due to size or configuration," said Bryans. Additionally, combination orthopedic products can pose a challenge to microbiological test systems, which must take into account the nuances of the devices, pharmaceuticals and/or biological components in one test design.
Innovations in products-especially biomaterials-require new approaches to packaging and sterilization. "The biggest challenge with the packaging and sterilization of biomaterials, such as polymers and bio-cohesives, is that these products are newer to the market so there is less knowledge about how to handle these processes," said Lucenti. "How will the materials react to the sterilization process? Will their chemical characteristics change? OEMs and outsourcing companies are still learning about how to ensure their products will still function the way they were intended to function."
Sparks reports there are more requests from clients to provide end users with full-procedure kits. These can range from providing accessory components like gauze and bandages to full barrier kits that contain gowns, masks, gloves, drapes, etc. "While we package components/instruments individually as needed, a large number of companies are seeking to combine these components/instruments with all of the other items needed for a procedure," said Sparks. "This makes it easier on the end user-they have everything they need for the procedure in one kit that is then directly charged to the patient. This also eliminates the cost of labor for pulling components, helps reduce waste, and makes tracking inventory easier."
One of the main challenges in packaging and sterilization is dealing with the weight of the products and the small batch sizes. Heavier devices and parts may penetrate even some of the strongest materials and require greater creativity in package design. For example, trauma nails (used for broken legs) are shaped more like metal projectiles than devices.
"In response to customer concerns with pin holing and film fracturing of pouches after they are subjected to the rigors of distribution, Oliver-Tolas has recently developed a stronger, higher-performing pouch that will help the customer's sterile barrier system survive the rigors of distribution," said Severin.
Latest advances in sterilization include new validation methods for lower doses in radiation sterilization, which opens up the possibility of terminal sterilization for products that might have been sensitive to traditional higher doses such as 25 kGy, including biologics or pharmaceuticals. "Parametric release for EtO sterilization is a process that is becoming more prevalent, and allows for immediate distribution of sterilized product without lot-release testing or lengthy quarantine periods," said Bryans.
One form of radiation sterilization, X-ray sterilization, is an emerging technology that has the potential to cause less damage to biological products with better uniformity of dose throughout a batch. An added benefit is the validation methods for X-ray are identical to those for gamma and electron-beam.
"The sterility assurance level guidelines, outlined in AAMI ST 67, provide options for SALs other than 10-6 (10-3, 10-4 and 10-5), which opens up the possibility of terminal sterilization for products that, to date, have not been able to withstand traditional 10-6 sterilization processes," Bryans added.
Another new technology Oliver-Tolas has developed is a seal adhesive called VisiSeal. "What makes this unique is that it reduces risk and cost by providing a visual check of seal integrity, which potentially reduces the cost associated with inspection, liability, rework, or scrapped product," said Severin. "It should also help reduce healthcare costs and infection rates because it provides quick verification of seal integrity, both at the packaging line and at point of use." The product is expected to be available in mid-2010.
Regulations and Standards
Although U.S. Food and Drug Administration (FDA) regulations haven't increased dramatically over the last few years, enforcement has, which means OEMs are becoming more conscientious about compliance. For example, ship testing (shake, rattle, and roll) has been taken to a new level. "One customer now drops a hammer in the center of the carton as a bridge impact test," said Lucenti. "To accommodate the new testing, we added a liner to allow for the force. These additional tests and accommodations add to the cost of a product."
Another challenge to packaging and sterilization processes are the recent changes in the standard for residual limits. "When utilizing gas sterilization, the allowable residual limits have recently decreased," said Sparks. "This change was put into place by ISO for patient safety. It can impact OEMs by forcing them to modify their packaging configuration or sterilization cycle in order to meet these limits."
Although recent changes in regulations and standards have not significantly increased the cost of compliance, most national and international regulations are moving steadily toward harmonization. This process will change to require investment, but will ultimately make compliance more efficient in the future.
"Meeting ISO 11607 comprehensive requirements for sterile medical packaging, for example, is not a simple thing to do," said Severin. "It is an excellent standard that has evolved over the past several years. The onus is on the MDMs [medical device manufacturers] to fully understand the standard and its intent, and apply it effectively to their products and processes. A thorough understanding of the applicable regulations and a comprehensive (not complicated) program to ensure compliance may be time-consuming at first, but will undoubtedly provide long-term payback in various forms, such as reduced costs, improved efficiencies, repeatable processes, and safe and efficacious products."
OEMs also are demanding more information from their packagers regarding the materials they use. They want to be sure the package meets all the requirements that are mandated by their own companies internally, as well as expected by their end users. "For example," said Schmitt, "customers are often making sure the product is free of BPA, DEHP and heavy metals. As a consumer, it's comforting to know companies are concerned about these chemicals, but the testing required and data collected is an additional cost."
Remember the Whole Supply Chain
It is essential that manufacturers of medical device products, while feeling the intense pressure to reduce costs, do not lose sight of seeking efficiencies across the entire supply chain, allthe way back to the raw-material providers-"the 'total system cost' if you will," said Severin. "Many times, under these cost pressures, companies try to reduce costs on only some elements of the chain, such as packaging materials, not taking into consideration the impact on other elements of the chain, resulting in catastrophic failures in the supply chain. This of course leads to recalls, rework, lost sales, lost customers, lost inventory, etc. This type of event very quickly erodes the purchase price savings realized earlier on."
"OEMs need to design their products with the terminal sterilization method in mind," added Howard. "Select materials that will be compatible with the process desired, and test them early. This way they have options in materials selection just in case a problem arises."
Lucenti suggests OEMs bring their outsource partners into the design process early. "An outsource partner is most effective when able to offer expertise regarding the pros and cons of packaging designs before packaging decisions are made and manufacturing has begun," he said. "The biggest benefit of including the outsourcing partner early on is the ability to side-step issues that might lead to missed deadlines, additional expenses and recalls."
Overall, packaging and sterilization processes have not changed much in recent years; however, outsourcing companies are working much more closely with OEMs to generate the greatest efficiencies with these processes (sometimes in unique or creative ways) that tend to be very customer-specific-for example, working on carton loading patterns as well as product loading patterns.
"By communicating early with their outsourcing partners, manufacturers can work with them to improve throughput for specific products and reduce costs," said Howard. "As product requirements become more specific, this communication can make the difference in whether or not a product can or cannot be sterilized with a given process, for example. By partnering with the manufacturer of a device, outsourcers will become better at developing processes that meet the unique requirements of new medical products."