Christopher Scott, Vice President, Eurofins Medical Device Testing10.05.17
Most discussions on packaging validations for medical devices begin and end with ISO 11607: Packaging for Terminally Sterilized Medical Devices, and are laden with interpretations of how the two parts of this standard apply best to the unique aspects of any given device and packaging system. Although compliance to the standard is a requirement for CE marking of products in Europe, and ISO 11607 is on FDA’s list of recognized consensus standards, meeting the requirements of ISO 11607 does not ensure the complete obligations of FDA’s Quality System Regulations are fulfilled. Section 820.130 of Subpart K (Labeling and Packaging Control) of the regulations state, “Each manufacturer shall ensure that device packaging and shipping containers are designed and constructed to protect the device from alteration or damage during the customary conditions of processing, storage, handling, and distribution.”
ISO 11607 deals with ensuring the primary sterile seal integrity of terminally sterilized medical devices, which in many cases, accurately represents the highest risk of failure as a product makes its journey from the manufacturer’s warehouse to the point of use. When considering a titanium or stainless steel implant or instrument, it is easy to expect that the weak link in a shelf-life study or transit simulation will be the plastic film or tray in which it is being shipped, or the heat seal that establishes the sterile barrier of the packaging.
In these circumstances, following the guidance of ISO 11607, and applying the appropriate ASTM, ISO, and ISTA standards will often satisfactorily address the packaging controls requirements of the Quality System regulation. As technology advances and designs of medical devices become more complex, however, the adequacy of adhering to this standard alone must be reconsidered. Beyond the necessity of ensuring an intact sterile barrier, the packaging is required to protect the functionality of the device itself.
A thoughtful, risk-based failure modes and effect analysis (FMEA) for complex (or even not-so-complex) assemblies should consider the following questions:
Shake, Rattle, and Roll
Fortunately, addressing these design concerns does not require reinventing the wheel. The same approach used to precondition and subject parts to simulated distribution cycles for validation of sterile barrier integrity can also be used to assess the functionality of a device. In fact, in many cases, the demands of functional testing may be less daunting if the impact of shelf-aging can be assumed to have a negligible impact on the product’s performance.
ISO 11607 serves as a guidance for subjecting packaged products to a range of conditions that might be encountered during storage and distribution, with the intent of subsequently assessing the primary seal integrity. This post-distribution analysis can include testing such as visual inspections (ASTM F1886), gross bubble leak testing (ASTM F2096), or dye penetration testing (ASTM F1929), to name a few.
The representative distribution simulation that is chosen to challenge the packaging will likely be the same whether the objective is to assess the sterile seal or product functionality, unless the FMEA identifies a unique concern that pertains to product design that is not expected to impact the packaging itself, such as rapid temperature fluctuations or extended vibration at a specific frequency (potentially inducing the loosening of mechanically fastened parts). This distribution simulation can follow well-defined conditions as outlined in ASTM D4169, or standard distribution cycles described by the International Safe Transit Association (ISTA). Both of these standards use a menu of simulation vibration and compression cycles aligned with typical distribution scenarios, as well as elements of induced rough handling.
Examples of these distribution simulations include ISTA Series 3A General Simulation Performance Tests for packaged products for parcel delivery system shipment weighing 150 lbs. or less, or ASTM D4169 Distribution Cycle (DC) 13, which simulates intercity air and motor freight (local, single package up to 150 lbs.) using large hydraulic platforms to replicate the amplitude and frequency of road and air travel. Rough handling simulations involve dropping packages according to specifically defined sequences from different heights onto the box faces, edges, and corners.
In the lineup of tests that are required to support medical device submissions and design history files, few have received such colorful monikers as have been assigned to distribution testing—shake and bake; drop and vibe; or shake, rattle, and roll. Despite the fanciful descriptions, these test standards prescribe a robust and disciplined methodology, which is well documented and accepted by regulatory agencies around the world.
Getting the Most from Distribution Simulations
When developing the final package validation protocol, it is often possible to assess both the sterile seal integrity and product functionality using the same sample. In order to realize the cost and time savings, it is important to select a seal integrity method that will not interfere with the functional assessment. For example, a pressure decay leak method (ASTM F2095) or bubble leak test may be preferred over a dye test if the seal test is to be followed by a mechanical performance test.
If package validation testing is outsourced to a contract laboratory, while functional testing is desired to be maintained in-house, then additional coordination and communication will be necessary to ensure testing protocols are appropriately cross-referenced and products are appropriately returned for subsequent performance testing.
This option presumes the testing is deemed a relatively low-risk validation and the distribution cycle is not expected to significantly impact the functionality of the device. If, however, a moderate or elevated concern exists over whether or not environmental or transit factors will impact a product’s performance, then it is prudent to perform these studies earlier in the design process, as part of the verification phase. In this case, a partial distribution cycle, or environmental treatment that emphasizes the conditions of concern can be investigated more robustly to support passage of an earlier design stage gate.
If a mechanical or product performance issue is identified during shipping simulations, the solution may be addressed through a packaging enhancement, such as a more rigid outer packaging shell, thermal insulating liner, more shock absorbent packing material, or the addition of a desiccant to the packaging system to reduce exposure to moisture for sensitive devices. Alternatively, the issue may force designers back to the drawing board to reevaluate the design of the device itself.
Label Integrity
One additional consideration for packaging validation that does not fall under ISO 11607, and is not addressed above, is the label integrity. Historically, the damage that two boxes or pouches rubbing against each other can cause to the label had been assessed by a simple visual inspection, whereby the primary endpoint was general readability or cosmetic acceptability. With Unique Device Identification (UDI) requirements, regulations demand that barcodes remain readable at the time of use. With the new UDI requirements comes an elevated need to assess the barcode scannability following distribution simulations.
Like the product functionality testing, barcode scannability and human readability testing can be performed as part of a standard ISO 11607 package validation protocol, using the same samples that will be used for seal integrity testing. For this testing, however, the non-destructive barcode testing would precede the seal integrity portion of the study.
Process Changes and Revalidation
Revisiting a package validation can be triggered by a number of factors and is most often associated with changes in packaging material suppliers, packaging line equipment or processes, or by a change in sterilization method. In light of performance considerations already discussed, it is important that any design or process changes to the device itself or the product labeling. Also consider whether that change may be sensitive to distribution chain rigors.
A robust packaging validation program during the design and development phase will provide a helpful basis for future design and process changes, which should require a straightforward comparison study to assess any potential effects resulting from the change.
Plan Ahead
It is important to incorporate package testing into the project plan early in the design process. But all too often, tremendous focus is given to the device itself, while package validation remains an afterthought. As a result, project timelines can be thrown off at the eleventh hour due to an unexpected failure during validation testing that could have been avoided with a quick screening test earlier in the design process. This planning should involve the full design team, including logistics, warehousing, marketing, and sales, in order to fully anticipate what conditions a product may be subjected to as it progresses through the distribution chain from the production site to the end customer.
Package validations are not only a regulatory requirement, but beyond that, the test methodologies employed can be a useful tool for ensuring a robust packaging system delivers the device sterile, intact, and in full functional condition for its intended use.
Christopher Scott is a vice president at Eurofins Medical Device Testing. With more than 25 years of experience in healthcare and medical device industries, Scott oversees operations for Eurofins Medical Device Testing. He has vast global experience in the development and commercialization of a broad range of medical devices. In his current role with Eurofins, Scott and his team serve as a partner for medical device companies in bringing their products to market through a comprehensive portfolio of testing services.
ISO 11607 deals with ensuring the primary sterile seal integrity of terminally sterilized medical devices, which in many cases, accurately represents the highest risk of failure as a product makes its journey from the manufacturer’s warehouse to the point of use. When considering a titanium or stainless steel implant or instrument, it is easy to expect that the weak link in a shelf-life study or transit simulation will be the plastic film or tray in which it is being shipped, or the heat seal that establishes the sterile barrier of the packaging.
In these circumstances, following the guidance of ISO 11607, and applying the appropriate ASTM, ISO, and ISTA standards will often satisfactorily address the packaging controls requirements of the Quality System regulation. As technology advances and designs of medical devices become more complex, however, the adequacy of adhering to this standard alone must be reconsidered. Beyond the necessity of ensuring an intact sterile barrier, the packaging is required to protect the functionality of the device itself.
A thoughtful, risk-based failure modes and effect analysis (FMEA) for complex (or even not-so-complex) assemblies should consider the following questions:
- Will the difference in the coefficient of thermal expansion between mating parts in my surgical instrument be impacted by a product that may be exposed to the back of a delivery truck in Arizona (potentially 140 degrees F) or a winter weekend in the trunk of a car in upper Michigan (potentially -40 degrees F)?
- Will continuous road vibrations, as my product is shipped from Boston to Los Angeles by truck, cause any of the threaded components in my assembly to back out?
- Will extreme temperature changes or high humidity cause my overmolded parts or surface coatings to delaminate?
- Will my packaging ensure that all electronic connections in my device withstand the impact or jarring of a cargo plane landing?
Shake, Rattle, and Roll
Fortunately, addressing these design concerns does not require reinventing the wheel. The same approach used to precondition and subject parts to simulated distribution cycles for validation of sterile barrier integrity can also be used to assess the functionality of a device. In fact, in many cases, the demands of functional testing may be less daunting if the impact of shelf-aging can be assumed to have a negligible impact on the product’s performance.
ISO 11607 serves as a guidance for subjecting packaged products to a range of conditions that might be encountered during storage and distribution, with the intent of subsequently assessing the primary seal integrity. This post-distribution analysis can include testing such as visual inspections (ASTM F1886), gross bubble leak testing (ASTM F2096), or dye penetration testing (ASTM F1929), to name a few.
The representative distribution simulation that is chosen to challenge the packaging will likely be the same whether the objective is to assess the sterile seal or product functionality, unless the FMEA identifies a unique concern that pertains to product design that is not expected to impact the packaging itself, such as rapid temperature fluctuations or extended vibration at a specific frequency (potentially inducing the loosening of mechanically fastened parts). This distribution simulation can follow well-defined conditions as outlined in ASTM D4169, or standard distribution cycles described by the International Safe Transit Association (ISTA). Both of these standards use a menu of simulation vibration and compression cycles aligned with typical distribution scenarios, as well as elements of induced rough handling.
Examples of these distribution simulations include ISTA Series 3A General Simulation Performance Tests for packaged products for parcel delivery system shipment weighing 150 lbs. or less, or ASTM D4169 Distribution Cycle (DC) 13, which simulates intercity air and motor freight (local, single package up to 150 lbs.) using large hydraulic platforms to replicate the amplitude and frequency of road and air travel. Rough handling simulations involve dropping packages according to specifically defined sequences from different heights onto the box faces, edges, and corners.
In the lineup of tests that are required to support medical device submissions and design history files, few have received such colorful monikers as have been assigned to distribution testing—shake and bake; drop and vibe; or shake, rattle, and roll. Despite the fanciful descriptions, these test standards prescribe a robust and disciplined methodology, which is well documented and accepted by regulatory agencies around the world.
Getting the Most from Distribution Simulations
When developing the final package validation protocol, it is often possible to assess both the sterile seal integrity and product functionality using the same sample. In order to realize the cost and time savings, it is important to select a seal integrity method that will not interfere with the functional assessment. For example, a pressure decay leak method (ASTM F2095) or bubble leak test may be preferred over a dye test if the seal test is to be followed by a mechanical performance test.
If package validation testing is outsourced to a contract laboratory, while functional testing is desired to be maintained in-house, then additional coordination and communication will be necessary to ensure testing protocols are appropriately cross-referenced and products are appropriately returned for subsequent performance testing.
This option presumes the testing is deemed a relatively low-risk validation and the distribution cycle is not expected to significantly impact the functionality of the device. If, however, a moderate or elevated concern exists over whether or not environmental or transit factors will impact a product’s performance, then it is prudent to perform these studies earlier in the design process, as part of the verification phase. In this case, a partial distribution cycle, or environmental treatment that emphasizes the conditions of concern can be investigated more robustly to support passage of an earlier design stage gate.
If a mechanical or product performance issue is identified during shipping simulations, the solution may be addressed through a packaging enhancement, such as a more rigid outer packaging shell, thermal insulating liner, more shock absorbent packing material, or the addition of a desiccant to the packaging system to reduce exposure to moisture for sensitive devices. Alternatively, the issue may force designers back to the drawing board to reevaluate the design of the device itself.
Label Integrity
One additional consideration for packaging validation that does not fall under ISO 11607, and is not addressed above, is the label integrity. Historically, the damage that two boxes or pouches rubbing against each other can cause to the label had been assessed by a simple visual inspection, whereby the primary endpoint was general readability or cosmetic acceptability. With Unique Device Identification (UDI) requirements, regulations demand that barcodes remain readable at the time of use. With the new UDI requirements comes an elevated need to assess the barcode scannability following distribution simulations.
Like the product functionality testing, barcode scannability and human readability testing can be performed as part of a standard ISO 11607 package validation protocol, using the same samples that will be used for seal integrity testing. For this testing, however, the non-destructive barcode testing would precede the seal integrity portion of the study.
Process Changes and Revalidation
Revisiting a package validation can be triggered by a number of factors and is most often associated with changes in packaging material suppliers, packaging line equipment or processes, or by a change in sterilization method. In light of performance considerations already discussed, it is important that any design or process changes to the device itself or the product labeling. Also consider whether that change may be sensitive to distribution chain rigors.
A robust packaging validation program during the design and development phase will provide a helpful basis for future design and process changes, which should require a straightforward comparison study to assess any potential effects resulting from the change.
Plan Ahead
It is important to incorporate package testing into the project plan early in the design process. But all too often, tremendous focus is given to the device itself, while package validation remains an afterthought. As a result, project timelines can be thrown off at the eleventh hour due to an unexpected failure during validation testing that could have been avoided with a quick screening test earlier in the design process. This planning should involve the full design team, including logistics, warehousing, marketing, and sales, in order to fully anticipate what conditions a product may be subjected to as it progresses through the distribution chain from the production site to the end customer.
Package validations are not only a regulatory requirement, but beyond that, the test methodologies employed can be a useful tool for ensuring a robust packaging system delivers the device sterile, intact, and in full functional condition for its intended use.
Christopher Scott is a vice president at Eurofins Medical Device Testing. With more than 25 years of experience in healthcare and medical device industries, Scott oversees operations for Eurofins Medical Device Testing. He has vast global experience in the development and commercialization of a broad range of medical devices. In his current role with Eurofins, Scott and his team serve as a partner for medical device companies in bringing their products to market through a comprehensive portfolio of testing services.
