The Packaging Puzzle: Finding the Right Fit
Packaging, sterilization and validation requirements all matter when developing a new device.
Like companies across many industries, manufacturers of orthopedic medical devices are under increased pressure to reduce costs and increase speed to market without compromising quality. The difference for medical device manufacturers is that their products require protection and sterility from the clean room to the operating room. Matching the device to the right packaging combination becomes paramount. It is similar to solving a puzzle. Each consideration, from product protection to packaging design and materials to sterilization method, has a relationship to or effect on at least one other aspect of the complete picture. Make a decision on one piece of the puzzle in a vacuum, and a product may take significantly longer to get to market—if it makes it at all. Add the important cost factor, and the conundrum becomes even more complex.
Developing a solution requires an OEM—collaborating with trusted internal and external partners—to basically work backwards. The process from manufacturing to finished goods includes cleaning, packaging, sterilization, shipping and delivery. To choose an effective packaging configuration, the OEM considers process elements in a different order: first, product protection, then sterilization, then packaging design and materials, and, finally, how each relates to the others. The end goal is a packaging option that provides a cost-effective, efficient solution that meets the highest standards of quality.
The Marriage Between Product and Packaging
An orthopedic medical device, such as a spinal implant or a knee replacement product, must arrive ready for use in a surgical procedure. Ensuring the integrity of the device requires that the product and its sterility be protected for the duration—from the point of packaging through the sterilization process, through shipping and over time. Medical devices to be implanted or used in surgery also necessitate packaging that allows for an aseptic presentation, one where the device can be removed from the packaging without the danger of contamination.
It goes without saying that OEMs know their products. Knowing the value of a product and its benefits to patients or in patient care is different, though, from understanding the product’s physical constraints with regard to packaging. According to Don Barcan, president and CEO of Donbar Industries, Inc., a Long Valley, NJ-based consultancy for medical device packaging, a full risk assessment is the first step in evaluating options.
“Understanding the fragility of a product is critically important, because this analysis will tell you how much protection the package must offer the device,” he said.
There are a number of questions to be asked:
• Does the device need to stay in place during transit?
• How heavy is the product?
• Is there a danger of sharp edges or components compromising the protective barrier?
• Will the device be damaged if it’s dropped?
• Is the device or a component more sensitive to one form of sterilization over another?
Sterilization is the next consideration to explore. The four major sterilization processes used by medical device manufacturers are steam, electron-beam radiation (e-beam), ethylene oxide (EtO) and gamma radiation. There are other methods of sterilization, such as pulsed white light, gas plasma and hydrogen peroxide, but these avenues are relatively new and/or are designed for smaller-batch sterilization.
Factors to be evaluated when determining a sterilization method range from the cerebral to the practical. One important issue is compatibility with the product itself and packaging materials. Another critical question is how effective each method will be in sterilizing the product. Efficiency also is a major concern, because this issue directly relates to the cost factor. Some sterilization methods cause delays in getting product to market, and some require small batch processing, increased precision and more handling—all of which are more time consuming. The aim for an OEM is to choose a sterilization method that passes the compatibility criteria and is commercially viable.
“OEMs have to understand how their products are going to be sterilized prior to the selection of packaging materials. They also need to know the kind of barrier characteristics that are required to maintain the integrity of their sterile product,” said Roger Allan, director of Research and Development for Mangar Medical Packaging in New Britain, PA.
Numerous technical factors must be considered when determining the best packaging and sterilization combinations for orthopedic devices. Photo courtesy of Millstone Medical Outsourcing.
Regularly used in hospitals for cleaning instruments and equipment, steam is one of the oldest methods of sterilization. The steam autoclaving process combines moisture, heat and pressure to eradicate microorganisms. The process is inexpensive, fast and leaves no residues. This method is particularly appropriate for metal products and parts because there is no degradation concern. The problem with steam comes with packaging, especially for medical devices that require an aseptic presentation. Few packaging materials can withstand the heat, moisture and pressure and maintain a strong, accessible seal.
E-beam radiation involves a beam—a concentrated and highly charged stream of electrons—generated by accelerating and converting electricity. When the product comes in contact with the e-beam, the electrons eliminate microorganisms. As a sterilization method, e-beam can be effective because it is precise and controlled. Drawbacks are that some plastics can be degraded by the process, products with high density may require a double dose of radiation and positioning of the product in the chamber can cause sterility issues because of shadowing, which occurs when the beam is blocked from reaching a portion of the product. Working out these issues can become really expensive, really fast.
Also commonly used is EtO, because this method is effective and less expensive than some others. Product packaged in a permeable material is placed in a sterilization chamber, where the product is subjected to EtO, a toxic gas that kills microorganisms. Then the product is moved to an aeration cell, where the EtO gas escapes through the permeable barrier. This out-gassing procedure can take anywhere from three to five days. In addition to increased turnaround time needed during the out-gassing period, another disadvantage to this method is that the medical device may absorb EtO. Special validations may be necessary to determine whether residuals can be reduced to acceptable rates.
Finally, many OEMs are turning to gamma radiation for sterilization. Gamma sterilization, which historically took a back seat to EtO, has increased in popularity because radiation can enhance speed to market. Products sterilized with radiation can be processed and shipped much faster, often right after sterilization. Two unwanted byproducts of gamma radiating certain plastics in an oxygenated environment can be the cross-linking of polymers and scissioning. Cross-linking of polymers can damage the surface of a device and can cause it to lose some of its flexibility and become brittle over time. Scissioning happens when the bonds of plastic molecules are broken. Lowering oxygen levels can combat both polymer cross-linking scissioning and their adverse effects.
Generally, two types of packaging materials are used for packaging medical devices: permeable and hermetic. Permeable materials, or those that are breathable, include Tyvek and medical-grade paper. Hermetic materials, or those that are airtight, include foil lamination and coated polyester. Each has benefits and drawbacks requiring evaluation for use in specific devices.
Before examining materials, OEMs will want to explore the options with regard to construction. The possibilities generally fall into three categories: pouches, bags and trays. Pouches and bags are flexible and come in a wide variety of shapes and sizes, from flat to gusseted pouches and from vented to header bags, which offer a combination of plastic for strength and a porous patch for permeation. Rigid packaging options, or trays, use either a plastic or flexible lid, prevent intrusion and are suitable for heavier products.
The next issue is package sealing, which is a critical part of the packaging process. Medical devices usually are packaged, sealed and then sterilized. Without a proper seal, the device arrives at its destination with compromised integrity. Two types of seals are a weld that typically is created by heat and a peelable seal that either adheres to a tray or can be pulled apart. The ability to create a strong and lasting seal on a pouch, bag or tray is another factor in choosing packaging material.
Tyvek, long the industry standard, replaced paper largely because the material offers greater puncture resistance and moisture repellency. Tyvek is porous, which is necessary for EtO sterilization, because gases are able to escape. Devices packaged in Tyvek pouches or in combination pouches or bags also can be sterilized using radiation. Remember, though, that the mix of radiation and oxygen can create problems for medical devices with plastic components because cross-linking and scissioning of polymers can occur. Therefore, an oxygen-permeable barrier material such as Tyvek is a poor choice for packaging these devices.
Foil lamination used in pouches, bags and with trays exhibits excellent protection properties and increasingly is used in medical device packaging. In addition to providing puncture resistance, foil lamination offers a significant barrier to moisture, oxygen, particulates and microbiological organisms. Foil lamination works well with radiation, especially for devices with plastic parts, because the laminated foil is virtually impermeable to oxygen molecules. Flushing and sealing a foil lamination pouch with nitrogen can reduce oxygen content to less than 1%, drastically reducing the likelihood of the cross-linked polymer and scissioning issues.
Packaging with a blend of materials that include polyethylene or polyester, whether in pouches, bags or as a tray lid, makes things just a little more complicated. Blend packaging provides a reasonable barrier of protection, but it is possible for the barrier properties to be insufficient and cause problems down the road. A blend pouch frequently is used because it is less expensive than Tyvek and is conducive to pulling a strong vacuum. A vacuum enables the device to be stabilized within the pouch, which reduces the risk of puncturing the packaging in transit and handling. Another packaging alternative, which provides extra quality control, is the use of a combination of materials. Packing a device in a foil lamination pouch within a foil lamination pouch (the foil-foil option) offers prevention to cross-linking and scissioning, the ability to use radiation and a strong barrier to intrusions. Using a foil pouch inside with a polyethylene/polyester blend pouch outside allows for the same security as a foil-foil combination at less cost. Again, vented and header bags, as well as trays with lids made from porous materials, provide the benefits of strength while facilitating gaseous sterilization.
In the end, packaging will be determined by a variety of factors. One more to consider is resistance to viruses and bacteria. According to Barcan, the issue begins at the molecular level. Breathable pouches, such as Tyvek and paper, are resistant to intrusion of bacteria but not viruses. Hermetic packaging, such as foil lamination, offers a higher level of protection from both bacterial and viral recontamination.
The Importance of Testing
Determining a packaging configuration is only the part of the work to be done in packaging medical devices. Validation and testing to ensure that the product reaches its final destination intact and sterile are of critical importance. Validation and testing requirements do not just apply to the packaging itself, but also to the potential dangers a packaged medical device might encounter along the way.
According to the introduction of ISO 11607-2:2006(E), Packaging for Terminally Sterilized Medical Devices, Part 2: Validation Requirements for Forming, Sealing and Assembly Processes
, medical devices delivered in a sterile state should be packaged in a way that guarantees sterility when the product enters the stream of commerce and maintains that sterility until the package is opened by the end user. Testing requires validation of a number of considerations. The packaging, or barrier system, must be able to maintain sterility, protect the physical properties of the device, pass seal-strength testing, fulfill packaging labeling requirements, offer an aseptic presentation when the package is opened and provide adequate protection to the hazards of handling, transport and storage. Validation, followed by the testing that proves the validations, is required for every aspect of the packaging and sterilization processes. From equipment installation to process quality, operational procedures and overall performance, ISO standards require comprehensive validations and testing to ensure that products are packaged, sterilized and delivered without damage or contamination. Validations, which are required to show repeatability and reproducibility, can take three months or longer.
Conforming to ISO 11607 standards is no easy task. In the end, validations can prove that an OEM made the right choices with regard to packaging, including sterilization, materials and seal. On the other hand, the validation process can send the manufacturer back to the drawing board to make different decisions. The goal is to establish a packaging configuration and validation plan that work together to meet the highest levels of quality while meeting cost and time factors. In addition to technical expertise, significant practical experience in developing and validating a packaging system is a must.
Putting the Pieces Together
One might think the job is over after a medical device has been designed, developed and manufactured. Experienced OEMs know that many more decisions await them before their product gets to market. In fact, some manufacturers have learned to incorporate issues around packaging and sterilization into the research and development process to head off future problems.
Perhaps the biggest challenge in determining a packaging configuration is not each independent decision that has to be made, but the fact that considerations overlap and are intertwined. Bringing a medical device to market is a time-consuming and costly undertaking. Nothing could be more damaging to a startup company—or even an established OEM—than getting too far down the road and then being required to change course because a packaging choice resulted in inferior quality. Carefully evaluating options by weighing pros and cons, working through all the repercussions and testing theories is the only way to truly establish a successful packaging plan.
Simplify the Packaging Puzzle by Choosing the Right Outsourcing Partner
While some large medical device OEMs choose to package and sterilize their products in-house, many companies work with outsource service providers to determine and fulfill packaging needs. The benefits of partnering with an outsourcing company can include savings of time and money and access to expertise. The biggest advantage, however, can be leveraging an outsource service provider’s experience to find the ideal packaging configuration—one that offers a cost-effective, efficient solution and meets the highest standards of product safety.
Medical device manufacturers are becoming more comfortable with tapping into the experience of outsource service providers to sterilize and package their products. Advantages often include more time and attention paid to critical core competencies. The question becomes, how does an OEM choose the best outsourcing partner?
First, determine if sterilization and packaging can be accomplished in-house. Equipment costs, which can be significant, as well as experience with a variety of sterilization and packaging combinations are two important factors in deciding between in-house processes and outsourcing. These considerations then are weighed against volume. For many companies, outsourcing is the best alternative because of the major expenses of purchasing equipment, hiring and training personnel, and/or engaging consultants with the right expertise.
Packaging can be complicated. Sterilization method, packaging materials, validations and quality concerns, shipping and distribution, as well as timing all must fit together to form the complete picture. Choosing the right outsourcing partner means assessing experience. Questions to ask include:
• Is the provider’s experience relevant to this particular packaging challenge?
• What types of packaging does the potential partner routinely provide, and who are its customers?
• What services and processes are completed by the outsourcing company (versus another party)?
• Will the provider’s services include comprehensive validation processes?
• Does the provider have in place an effective quality assurance plan and team to ensure the highest level of quality?
• Does the provider conform to all relevant federal guidelines and standards? Does the firm’s quality track record reflect these standards?
• What is the vision for the company? Is contract packaging the biggest part of the plan?
OEMs must view the outsourcing company as a strategic partner. Beyond just the basics, an outsourcing partner protects the OEM’s interests by making quality the highest priority; is knowledgeable about the OEM’s business and the market; is resourceful in developing solutions to packaging challenges; and identifies innovative ways to streamline processes. The best outsourcing partner is focused on continuous improvement and able to grow both in capabilities and capacity.
Garrett Douglas is vice president of New Business Development for Millstone Medical Outsourcing. Millstone Medical, outsource partner to leading orthopedic companies, is a provider of aftermarket services, startup solutions and contract packaging services for medical device manufacturers worldwide. For more information, call (508) 679-8384 or visit www.millstonemedical.com.