Medical Device Packaging and Sterilization: What you need to know to protect your product By Wanda I. Colón-Rivera, PE ASQ-CQA, CMQ/OE, CSSBB When a medical device manufacturer designs and develops an effective, safe and reliable, state-of-the-art medical device that will positively impact many lives, their eagerness to package it up and ship it out is understandable. What they may not be aware of or have inadvertently overlooked is that their product s packaging and sterilization needs go through an extensive validation process. And the FDA has stringent standards about how this is done. The packaging system for a sterile medical device must serve two primary purposes: (1) create the sterile barrier for the device, and (2) protect and safeguard the device s functionality. The technical process required to properly validate medical device packaging can shock and frustrate some companies, especially if they are new to the process. For example, as part of the FDA s 510(k) clearance process, packaging validation must be in accordance with ISO 11607. To demonstrate conformance, packaging engineers need to conduct three very involved validations: 1. Packaging System Performance This validation is used to establish the capability of the packaging system to ensure that it maintains its sterility when stresses are imposed on it by the manufacturing process, sterilization, handling, storing and shipping conditions. 2. Stability testing This test must be performed using real time aging and is used to demonstrate that the sterile barrier system maintains its integrity over time. When accelerated aging is used, real time and accelerated aging test should be done parallel to one another. 3. Validation of the Packaging Process This process validates the packaging process to assure that the sealing process and critical parameters used at the packaging facility will produce a process that is in control, and capable of producing a package system that meet the design specifications. Process validation shall include as a minimum Installation Qualification (IQ), Operation Qualification (OQ), and Performance Qualification (PQ). While packaging validation is an incredibly important step in the process of ensuring that the device will remain sterile and protected until it is ready for use, it s still not the last step. The device must also be validated by a sterilization specialist to ensure that, after the device is packaged and sealed, any microbes that may still be present on the product after packaging have been neutralized.
The FDA has several consensus standards for sterilization validation, such as Ethylene oxide (EtO), radiation (gamma, E-beam, x-ray), and steam. The standard that is used depends on the sterilization method chosen for the device. For example, for radiation validation (gamma), the FDA uses consensus standard ISO 11137. For EtO validation, the FDA uses consensus standard ISO 11135. Complying with the FDA s standards for packaging and sterilization requires specialized skill-sets, resources, time, and money. Most medical device start-ups cannot afford to hire engineers with these specialties, nor does it make business sense for them to do so since their packaging will stay the same for many years after it s validated. This is why most medical device start-up companies seek the expertise and capabilities of an experienced contract packaging company that also has access to sterilization validation resources. Partnering with a packaging and sterilization outsourcer can have substantial benefits to both small medical device start-ups and large, well-established manufacturers. To safeguard and maximize these benefits, there are also important road blocks medical device manufacturers need to be aware of so that they can avoid them during their packaging and sterilization validation process. Benefits of Contract Packaging and Sterilization Reduces cost and overhead pressures - All sterile packaging must be done in an ISO-controlled environment or clean rooms. A clean room is a room in which the concentration of airborne particles is controlled to specified limits. Creating and maintaining this environment and building a clean room is a costly, high-overhead endeavor that demands significant human resources. For example, tests must be conducted on a frequent basis to monitor the environment and packaging processes to ensure that the device will remain sterile. This includes tests to monitor seal strength, bioburden (population of microbes on or in a product or package), airborne particles (including viable particulate), temperature, humidity, water quality, etc. The significant resources required to have the proper ISO-controlled environment in place is cost-prohibitive and beyond the scope of what is manageable for some medical device companies. Contracting with a medical device packaging company, saves manufacturers from having to build expensive infrastructure, hire engineers with expertise in packaging and sterilization, or concern themselves with maintaining an environment that may or may not be used at full capacity. Access to better pricing Medical device manufactures can benefit from better pricing by outsourcing sterile packaging. Sterile packaging outsourcing partners have the ability to combine and pool similar products for batch processes like sterilization. This eliminates the amount minimum lot fees a small volume manufacturer would be charged for these services.
This also applies to packaging materials (e.g. nylon pouches, shipping boxes, blister trays, etc.). A contract packager purchases packaging materials in large quantities, which gives them access to better pricing per unit a savings that they can pass on to their customers. Reduces handling, lead times and Work in Process More often than not, sterile packaging outsourcers have additional capabilities that a manufacturer can take advantage of in addition to sterile packaging. The more capabilities a packaging facility has, the more value it can provide to a company looking to outsource packaging. For example, some machining facilities have the capability to fully inspect their finally cleaned product, package it and sterilize it. In this scenario, the amount of handling, work in process and lead times is improved greatly. Reducing handling is of utmost importance when the finished product is highly polished or has porous coatings applied to it. Less handling also minimizes the potential for contamination and bioburden on the product to be sterilized. By removing queue time and transportation, the value stream becomes more efficient and accelerates time to market. Road Blocks to Avoid When Outsourcing Packaging and Sterilization 1. Don t Forget about packaging. It s not uncommon for medical device manufacturers to be so focused on developing a reliable, high-quality device that will be cleared by the FDA that packaging design comes as an afterthought in the design process. It s usually late in their product development process when the manufacturer finally approaches a packaging and sterilization outsourcer. Consequently, when the manufacturer learns that these additional steps will not only be costly, but also take four to six more months to complete, they are understandably dismayed. To avoid this road block, it s essential to consider the sterile packaging validations that will be required for your device concurrently with the design and development of the device. 2. Insufficient outsourcing resources. Any time a medical device manufacturer transfers a part (or all) of their packaging operation to an outsourcer, some aspects of the sterile packaging system need to be revalidated. If the contract packager doesn t have the expertise or internal resources to properly validate the process, then the manufacturer must send their own engineer to that packaging outsourcer to do it. In addition to consuming the manufacturer s time and resources, it also nullifies a key reason for outsourcing the packaging process in the first place. The same logic applies to sterilization validation. If a manufacturer outsources their packaging, the device will come into contact with different bioburden.
Therefore, an outsourcer needs to have sufficient knowledge, expertise, and testing capabilities to confirm that the sterilization validation is still adequate. Otherwise, the process will not conform to the FDA requirements. To avoid this roadblock, it s crucial to work with an outsourcing partner that has the in-house resources and expertise to conduct sufficient packaging and sterilization validations. 3. Overlooking the requirements for revalidations The FDA requirements for sterilization revalidations are often a surprise to medical device manufacturers. The initial thinking is that the process is completed once the initial product has been validated for sterilization. The reality is that sterilization re-validations must be done every three months as required by ISO 11137, and bioburden needs to be monitored in accordance with ISO 111737 to capture seasonal changes (usually every three months). At initial sterilization validation, one of the most common considerations when selecting a master product to validate is device size. However, because the largest-sized product is often a book end product, with low demand, the manufacturer is unlikely to hold a significant quantity of it in inventory. For example, if a manufacturer s largest hip stem is a size 10, the size 10 would be the master product used in the sterilization validation to represent all the sizes in the family of hip stems. While the manufacturer awaits FDA clearance (which could take six months or more), they are likely to stockpile their higher demand, mid-sized hip stems (e.g. size 4, 5, and 6) and keep only a limited number (e.g. 20) of lower demand size 10 hip stems in inventory. In some instances, by the time the manufacturer receives FDA clearance, the sterilization validation is due for revalidation and the master product (the size 10 hip stem) needs to be available. In order to support that the sterilization validation is still adequate, thirty size 10 hip stems may be needed for the revalidation. However, if the manufacturer only has twenty units available in their inventory, the entire launch plan may be delayed until the full quantity needed for revalidation becomes available. To avoid this road block manufacturers must take into consideration the amount of inventory needed, not only to satisfy forecasted demand for the product, but also for any additional testing required by regulations. Prepare and Participate While not always easy to comprehend, the FDA website and consensus standards database is a good starting point for medical device manufacturers to learn about the requirements for packaging and sterilization validation. Professional organizations,
industry consultants, and testing laboratories are other helpful resources. Before a manufacturer contacts a contract packaging and sterilization partner, it s important that they be prepared to answer some important questions, including: - Where is the device at in the design process? - When is the device planned for market launch? - Is there an existing packaging design? If yes, has the packaging design been validated? If no, does the manufacturer need the contract packager to design the package? - Is the device already on the market? - Does that device already have the current design validation? - What processes, materials and consumables are used for manufacturing the device? - Is the device sensitive to light, temperature, oxygen or other factors that may impact its functionality? If the manufacturer is not prepared and well equipped to deal with the realities, criticality, and complexity of packaging and sterilization, it can derail their product launch. This is why it s essential for the manufacturer understand what the regulatory requirements are for their device and to ask the right questions of their potential outsourcing partner. There should be few, if any, surprises about costs and the time it will take to complete the packaging and sterilization validation testing. To help facilitate a transparent and straightforward validation process, ensure that the contract packager not only understands the specific requirements of the medical device industry and has the resources and capabilities to meet them, but is a partner that you feel you can trust to safeguard the integrity of your medical device. Wanda I. Colón-Rivera is the Packaging and Sterilization Manager at Orchid Orthopedic Solutions and is an active member of AAMI, ASQ Certified Quality Auditor, Certified Six Sigma Black Belt, and Certified Manager of Quality and Operational Excellence. Orchid Orthopedic Solutions is a Holt, MI-based contract sterile packager, designer, manufacturer of implants, instruments and innovative technologies for the orthopedic, dental and cardiovascular markets.