Packaging and Sterilization validations are a critical step in the development and manufacturing of medical devices, as they ensure patient safety, regulatory compliance, product quality, and the trust of healthcare providers and consumers. The purpose of Packaging validation is to ensure that the packaging system effectively protects the medical device throughout its intended shelf life and distribution process. This is essential to verify that the chosen packaging materials and design maintain the device's integrity, sterility, and functionality. The sterilization validation ensures that the chosen sterilization process effectively and reliably eliminates or reduces the microbial load on the device to an acceptable level. Sterilization validation confirms that the device is safe for patient use and meets the required sterility assurance levels. Maintaining sterility is crucial to prevent infections and ensure the safety of patients during medical procedures. Together, packaging and sterilization validations are an integral part of the overall quality assurance process in medical device manufacturing and distribution.

There are specific standards established for packaging and sterilization validation for medical devices. A few important standards that govern these aspects are ISO 11135:2014 (Sterilization of health care products - Ethylene oxide) and ISO 11137 (a series of standards that provides guidance on radiation sterilization methods), and ISO 11607-1:2020 (Packaging for terminally sterilized medical devices). Manufacturers of medical devices must adhere to these standards to ensure that their packaging and sterilization processes are validated, controlled, and comply with industry standards and FDA requirements. Non-compliance with these regulations can result in patient harm and regulatory actions including recalls, warning letters, fines, or other enforcement measures.

Although the current standards offer standardization and direction, sterility and packaging issues may still lead to recall if not taken seriously. There are several common mistakes that are made when creating and testing a packaging system for medical equipment that has undergone terminal sterilization. Understanding these mistakes and how to avoid them is crucial during the process validation lifecycle of a medical device.

Sterility and Packaging are Related

Devices intended for terminal sterile packaging must maintain their sterility throughout the entire labelled shelf life. Contamination during manufacturing, packaging, or handling can lead to recalls due to risk of infection, which is why maintaining the sterile barrier from the moment a product is packaged to the time it is opened in an operation room is so important.

Loss of sterile integrity is the most frequent failure mode that occurs when packaged medical equipment is subjected to production, handling, and storage. A product’s sterility is often compromised by pinholes, slits, rips, and tears in pouch packing, which can happen because of shipping and handling, but also from poor pack-out procedures. During shipment, impacts from dropped packages, routine handling errors, the vibration forces produced by the movement of trucks over pavement and the changing pressure during air shipment all subject the package to damage. On the manufacturing floor, breaches in the sterile barrier can be caused by pinholes and microtears as a result of sharp edges on the device or a die card, staples on an information booklet, or more commonly, by folding or creasing the pouch when placing inside the device’s box.

For these reasons, it is important to perform a robust packaging validation that evaluates your product after it has been subjected to the validated assembly and pack out procedure so there are no surprises down the line. ISO 11607, Packaging for Terminally Sterilized Medical Devices specifies requirements and test methods for materials, pre-formed sterile barrier systems, sterile barrier systems, and packaging systems intended to maintain the sterility of terminally sterilized medical devices.

Optimize Testing Process

With the focus on creating a new product and validating the manufacturing process, packaging and sterilization often fall on the backburner. Many device companies are unaware that testing package systems is necessary, and some are even unaware that ISO 11607 and FDA sterilization guidance exists. Just like with the medical device itself, a product’s packaging takes time and effort to develop, purchase, and validate. When packaging and sterilization is left to the end of the manufacturing lifecycle, it’s tempting for businesses to take shortcuts by attempting to finish package validation without adhering to accepted scientific procedures. Cutting corners to save money and effort can not only can not only lead to a non-sterile or damaged product reaching the consumer, but more than likely will lead to longer development time and higher overall validation costs when a component of the rushed package system inevitably fails during validation. Each validation error necessitates retesting, which requires more time, material, and money. As an added bonus, with the adequate planning, you may be able to leverage dunnage material or perform multiple tests on a single unit (as long as proper justification is provided) which can save both time and money!

If the right work had been done in advance, any failed package system properties would likely have been found in preliminary testing projects before validation. Common prequalification tests that should be conducted to find any potential design or manufacturing issues include seal strength and seal integrity tests and preliminary shipping tests to reveal any flaws in the manufacturing or packaging process so corrective action can be taken ahead of time.

Be Prepared for Worst-Case Scenarios

It’s important to think about the many ways in which your product might be shipped when designing your packaging validation study. Let's say for example that the product is assembled and packaged in-house, then shipped to the sterilizer on a pallet, but is sold to customers in boxes of 5. Each of these configurations and shipping instances has the potential to damage the product and/or cause a breach in the sterile barrier, so it is imperative that each configuration is considered when designing the packaging and sterilization validations. While a prequalification test may be considered time consuming, running short tests on numerous configurations can help identify the worst-case package configuration. The last thing you want to do is send out an entire lot of finish goods for your packaging validation study, only to find out the sharp die card punctures the pouch during transit. By taking the time up front to determine the worst-case scenarios and rule out preventable errors (like sharp edges), you will gain the confidence that package configuration will pass validation testing. Additionally, by determining the worst-case scenario, you may be able to leverage the existing validation to reduce the testing required for additional shipping configurations.

Establish a Solid Protocol for Seamless Execution

An approved validation protocol is required before validation begins. This protocol provides a detailed plan of the testing process that specifies the test's objectives, parameters, production settings, and acceptance criteria. A validation process is comprised of several unique process qualifications that make up the entire package process system. The final package design, the packaging materials, and the capability to sterilize the product inside its box are all included in this entire package process system. One area of the protocol that may be overlooked is the need for a thorough investigation into the sterilization method will need to be performed.

The sterilization method selected will depend on the materials, construction, and packaging of the product, and significant effort should be put into weighing the pros and cons before pursuing one. For example, on one hand Ethylene oxide (ETO) sterilization may be a great option for a product because it is safe for a wide range of materials, including heat-sensitive materials, and it does not require an intricate dose map (like gamma radiation), but it is unable to penetrate closed, non-porous cavities and requires a time-consuming aeration process to remove the residual toxic gas. On the other hand, gamma radiation leaves no residual toxicity and requires no aeration but can damage both the product and its packaging and requires dosimetry studies to achieve uniform dose distribution, which can be costly and time consuming to configure. Improperly sterilized devices could degrade over time, affecting their performance and potentially leading to device failures during use.

A thoughtfully designed and well-written procedure is the first step in the validation process, which demands meticulous planning and preparation. The absence of written procedures can lead to inconsistent practices and difficulties in replicating successful validation processes. Some areas to consider are:

• What equipment will be used to package the product? All equipment and procedures must be validated to ensure consisted results.
• What sterilization method will be used (gamma, Ebeam, ETO, etc.)? In addition to validation, the effectiveness of the sterilization, how will this affect the integrity of product and its packaging?
• What are the sample sizes required to prove with statistical confidence that you have met the product requirements and SAL acceptance criteria?
• How will the product be shipped (quantity, configuration, etc.)? What materials will be used and what methods will be followed to ship the product?

Not Involving Relevant Stakeholders:

Collaborating with all relevant stakeholders, including packaging engineers, quality assurance personnel, and regulatory experts, is crucial for a comprehensive validation process. Failing to involve key stakeholders may result in oversight and inadequate validation strategies. While it may seem like engineering has packaging and sterilization covered, here are a few instances to consider:

• Does the marketing or clinical team intend to include additional instructions or labels on or inside of the final packaging? If so, how will this affect your sterilization validation, protocols, and shipping configuration?
• Is the sales team willing to stick to only selling the product in quantities of 5, or do they want to sell any quantity that will satisfy the customer? Final product must be shipped in a validated configuration, otherwise you risk delivering damaged or non-sterile product to the customer.
• Sterilization companies may charge by piece or by lot. They may also require a minimum monthly volume to reserve routine sterilization at their facility. Also, depending on the sterilization method chosen, the shipment quantities may need to remain consistent. It is important to consult with multiple stakeholders to determine the frequency and size of shipments that are made to the sterilizer to maximize the space in the sterile chamber, and/or to establish the most cost-effective solution.

Maintaining a Validated State

Any changes to the packaging materials, design or process should be subjected to change management and re-validation consideration.

Conclusion

The packaging and sterilization of a medical device should be treated with the same level of attention as the development of the device itself. To avoid these common mistakes, medical device companies should meticulously plan and execute their packaging and sterilization validation processes, utilizing appropriate sample sizes, conducting comprehensive environmental testing, and considering worst-case scenarios to ensure the reliability and effectiveness of the medical device. Additionally, staying up-to-date with regulatory requirements and involving all relevant stakeholders can contribute to a successful packaging validation process.

When it comes to packaging and sterilization validation, many manufacturers unknowingly stumble upon common mistakes. Unlock Packaging and Sterilization Success! Avoid Common Pitfalls with Compliance Group Inc.

Choose Compliance Group Inc to elevate your packaging and sterilization validation practices. Contact us at [email protected] to ensure a successful and compliant validation process that puts you on the path to manufacturing excellence.