As with many industries, packaging is not typically at the forefront of production, but is an extremely important component to the overall marketability and durability of a product. In the medical device industry, this is no different. In fact, without proper packaging, a high risk is posed to the patients’ health, with the possibility of infection or in the worst case, death. With such risk involved, this is why the medical device industry is among the highest regulated for packaging. Aside from patient health, effective packaging is a large contributor to the overall success of a company. When considering the high volume of products produced, an FDA recall related to packaging has the potential to cost a company millions of dollars. An instance in which thousands of products are recalled due to faulty packaging affects current revenue for a company; it also affects the overall reputation of a company in the healthcare industry.
There is no doubt packaging is an extremely important asset to a medical device. Regulatory authorities actually consider the sterile barrier system as a component of the medical device. With defective packaging, a medical device is rendered useless. Although medical device packaging has been regulated for many years, the most widely accepted standard currently being followed is ISO 11607. Introduced in 2006, this standard was accepted by the international community and the FDA as the standard for terminally sterilized medical devices. All areas of medical device packaging including materials, accepted test methods, process requirements, and shelf life requirements are included in this standard. ISO 11607 is the touchstone text for medical device packaging.
This report will explore the validation requirements of packaging for terminally sterilized medical devices through ISO 11607. The intended audience is for those who might be a recent graduate taking on a new role as a packaging engineer in the medical device industry, medical professionals curious about what processes take place to ensure their product arrives safely, or those who might already be a packaging engineer but would like to know more about the medical device industry.
ISO 11607 is divided into two parts: 11607-1 and 11607-2. ISO 11607-1 describes the validation requirements of the package integrity through distribution, storage, and sterilization. ISO 11607-2 describes the validation requirements for forming, sealing, and assembly processes. Having knowledge of the definitions of these key terms given by ISO 11607 will help in understanding the content of this report.
Sterile Barrier System (SBS)- A sterile barrier system is defined as the “minimum package that prevents ingress of micro-organisms and allows aseptic presentation of the product at the point of use.”
Protective Packaging- A “configuration of materials designed to prevent damage to the sterile barrier system and its contents from the time of their assembly until the point of use.”
Packaging System- A “combination of the sterile barrier system and protective packaging.” The packaging system must minimize potential safety hazards by: 1) maintaining sterility of the packaged device; 2) providing protection against biological risks; and 3) preventing damage that could lead to device malfunction.
When designing a packaging system, there are many points to take into consideration. At minimum, a sterile barrier system must allow sterilization, provide an acceptable microbial barrier, and allow for aseptic presentation. The intended use, shelf life, and sterilization methods for the device are all key factors. As required by ISO 11607, each part of the packaging system must be validated to prove it performs in the way it is described by the manufacturer. The performance of a sterile barrier system is validated by performing strength and integrity. Seal strength is defined by ISO 11607 as the mechanical strength of the seal. This is referring to the force required to separate two components of the package that form together to produce a seal. Seal integrity is defined by ISO 11607 as condition of the seal, which ensures that it presents a microbial barrier to at least the same extent as the rest of the packaging. The seal strength alone is not a good representation of the overall integrity of the package. For example, the mechanical strength of a seal does not detect a pinhole in the package. While a strength test might yield an accepted value, there is still possibility that a channel or pinhole could have existed in the seal. Integrity testing provides methods to detect micro-channels and other defects such as pinhole leaks in the package. This is why both strength and integrity testing must be performed to validate packaging systems. The following table lists the most common and accepted test methods for testing the integrity and strength of the sterile barrier system.
Stability testing must be performed to demonstrate the ability to maintain a sterile barrier over time. For example, if a medical device company claims their packaging system will maintain a sterile barrier for a 10-year period, there must be evidence to back this up. This is completed through both real-time and accelerated aging studies. Real-time aging samples are created and stored in ambient conditions for up to 10 years. Once time has elapsed, strength and integrity tests are performed on the samples to validate the sterile barrier system has maintained the standards after sitting on a shelf for the specific amount of time. This is a lengthy process and could drastically increase the time it takes for a product to enter the market. So much that the product might be outdated by the time it is cleared to enter the market. It is for this reason, accelerated aging is an acceptable method, pending the test results of real-time samples. Accelerated aging is a process in which samples endure numerous cycles of high heat and moisture in environmental chambers to simulate an extended period of time on a shelf. Test results from accelerated aging are accepted until the point the real time samples are ready to be tested. For example, strength and integrity tests for a 3-year accelerated aging test will suffice validation requirements until 3 years from the test start date. At this time, testing on the real-time samples will be conducted and replace the results of the accelerated aging samples. To keep the samples in unison, real-time and accelerated aging should begin simultaneously.
As stated in ISO 11607, one goal of the packaging system is to maintain sterility up to the point of use. As we all know, the rigors of distribution can affect the performance of the contents in a package. ISTA-3A is an accepted method for simulating the distribution environment. ISTA- 4AB is also an accepted method for simulating the distribution environment. ISTA- 4AB is used as the test method for simulating distribution along a specific route. For example, if a product is known to only ship from one specific location to another, a unique testing profile is created for that route. Drops and vibration can shift the product around inside a package causing the possibility of tears, holes, or punctures in both the body and seal of a package. After all distribution testing is completed, the integrity and strength of packaging systems are tested.
As required by ISO 11607-2 all packaging processes related to the assembly of the packaging system must be validated. As a minimum the following qualifications are used to validate the packaging process: Equipment Installation Qualification, Operational Qualification, and Performance Qualification.
Equipment instillation qualification (IQ) is the validation requirement for any equipment used in the process of forming the packaging system. Items such as controllers, sensors, and displays must all be validated to ensure the equipment operates as intended. Also, proper operator training and maintenance schedules must be documented for each piece of equipment used in the process of forming the packaging system.
Operational Qualification (OQ) is the validation requirement used for establishing the capability of parameters as determined by the manufacturing limits. For example, the nominal settings for sealing a pouch may be for 6 seconds, 130º F, and 30 psi. An OQ will validate the process at limits above and below these values. By establishing upper and lower limits, any combination of time, temperature, and pressure is validated to produce an acceptable seal.
Performance Qualification is the validation requirement used to show a process is capable of consistently producing acceptable seals. This is performed by sealing a large number of samples at predetermined limits as specified in the OQ. Strength and integrity testing are performed on all samples to ensure the process is capable of consistently producing acceptable seals.
It is safe to say the medical device industry is among the highest regulated for packaging. However, when considering the high-risk level, the regulations are in the best interest of all parties involved with a medical device. There are many factors that play a key role in designing packaging systems for medical devices. It can be an extremely complicated and time-consuming process to ensure the packaging system is best suited for a medical device. A packaging engineer in the medical device industry must always remember their ultimate goal is to ensure patient health by providing a packaging system that can maintain sterility until the point of use.
References
BS EN ISO 11607-1:2017 – Packaging for terminally sterilized medical devices. Requirements for materials, sterile barrier systems and packaging systems
ISTA Series Test Procedures – International Safe Transit Association Preshipment Test Procedures
Nolan, Patrick J. “Sterile Medical Device Package Development.” Digital Engineering Library, McGraw-Hill, 2004, www.unhas.ac.id/tahir/BAHAN-KULIAH/BIO- MEDICAL/NEW/HANBOOK/23_Sterile_Medical_Device_Package_Development.pdf.
“Validating Medical Device Packaging.” Library.ul.com, UL, 2016, library.ul.com/wp- content/uploads/sites/40/2016/12/Validating-Medical-Device-Packaging-final.pdf.
