IVD devices are an important part of healthcare. These devices typically contain a sample collection area on which chemical reagents or biologically active proteins react, sometimes electrochemically, with the sample to produce something that can be measured optically or photometrically. By virtue of their critical function in analyzing samples ranging from urine, saliva, and blood to swabs of cellular matter at home or in a laboratory, their reliability must remain intact. This integrity must extend from the production line through distribution, until the package is opened for use anywhere in the world.
|Fit-In sorbents can be custom manufactured in various shapes and sizes to fit into a device.|
IVDs are highly sensitive to changes in their packaging environment. The pathways to deterioration in IVD devices typically include changes in their chemical, physical, and biological characteristics.
Moisture is typically the biggest degradation threat to IVDs. The largest single contributor to moisture ingress is via imperfections in the seal of the packaging that is supposed to protect the IVD device. Moisture can also enter the sealed package environment (or headspace) from the actual IVD device, through the packaging material, from the environment at the time of packaging, and from additional internal packaging or printed materials. To a lesser extent, oxygen and hydrocarbons also pose both a threat and a potential challenge to IVD devices.
Establishing the correct level of control of these elements in the headspace of IVD device packaging is often required to ensure the integrity of reactants and substrate. Should one, two, or all of these elements be present inside the packaging in a critical amount, they could either damage the device significantly or negatively affect the chemical reaction for diagnostic purposes. This could result in inaccurate and inconsistent test results. For example, a diabetic person using a compromised test strip to test his/her blood glucose levels could receive a false high or low blood glucose level reading, triggering an inaccurate administration of insulin.
It is precisely this type of risk that illustrates the minute margin for error in selecting active and static packaging for IVD devices. This places a huge amount of pressure from both product effectiveness and accuracy perspectives on the IVD manufacturer and packaging engineer. Choosing the correct desiccant or sorbent at the right time will give the IVD manufacturer a strategic edge because it helps get its product out to its target market on time with the desired stability profile and related shelf life. In addition, the correctly configured desiccant and packaging will extend the reach and robustness of the manufacturer’s supply chain, giving it a business and brand building edge it needs.
As an example, excessive desiccation of some IVD products can change the physical performance of the device. In one brand of test strip, a hydrophilic material is used on the top layer of the reagent pad to quickly disseminate the sample across the test-strip substrate. Excessive desiccation proximal to the substrate can change this material from being hydrophilic to hydrophobic, slowing the physical reaction time of the sample with the reagent. In an industry fixated on fast reaction times, an acute understanding of sorbent type and position in the packaging can be critical.
The key to choosing the correct sorbent is understanding the nuances of the IVD device to be packaged as well as the applications for which it will be used. The uniqueness and specificity of each device could make an off-the-shelf solution outdated and ineffective. Empirically based registration stability testing will continue to bear this out.
The IVD industry is closely regulated and compliance is critical. IVD manufacturers are compelled to ensure that their devices are chemically stable and offer consistent and accurate results. Nothing gets to market that doesn’t function reproducibly as verified by stability and functionality testing, as well as FDA review, approval, post-approval, and market monitoring. These strict requirements indicate that IVD manufacturers cannot source a sorbent based solely on price and volume discount. It is also important to realize that no two IVD devices are the same. Even if they are manufactured by competing companies to perform the same function, they will not only be shaped differently but they will also use different reagents, substrates, plastic materials, and packaging. All these aspects play a key function in determining the makeup of a sorbent.
While the management of moisture in the device and package headspace remains a central concern in IVD products, oxygen and hydrocarbon management can also play a significant role in ensuring IVD product stability.
In some circumstances, a highly complex sorbent is required to both manage and balance a delicate environment that contains oxygen, moisture, and hydrocarbons. This intelligent sorbent is smart enough to remove oxygen from the sealed packaged, manage humidity, and absorb the hydrocarbons. Establishing a steady-state relative humidity condition inside a package or device headspace avoids the denaturing of biologically active proteins via excessive desiccation while preventing the hydrolysis associated with elevated humidity conditions. A one-size-fits-all approach to packaging protection is clearly not a viable strategy. An active packaging strategy must be intelligent, and it must be optimized based on the specific application. It is essential that the entire lifecycle of the device from manufacturing to end use be taken into consideration.
This poses a significant challenge: How do you make sure that you choose the correct sorbent for your IVD device to ensure that the stability and efficacy of the device as a whole and its individual components are maintained?
Historically, basic calculations were made for products requiring a sorbent selection for registration stability lots. A sorbent-ranging study was then performed to determine whether or not the recommended desiccant and its quantity were correct.
Today, of specific importance to research and development chemists, packaging engineers, and the manufacturers of IVDs is the growth of pseudo-empirical modeling as a means by which IVD manufacturers can quickly screen for the most promising active packaging stability solutions for their devices. This quality-by-design (QbD) service is already well established within the pharmaceutical industry. Sophisticated pseudo-empirical modeling involving complex and detailed mathematical formulations is being used to scientifically determine the best sorbent to protect the integrity of an IVD device throughout its lifecycle.
The modeling predicts the internal conditions of an IVD product package based on a given set of external conditions and selected input criteria. The modeling is based on the integration of internal and external equilibrium relative humidity conditions with time, and the absorption profiles/isotherms of the desiccant and IVD device components or chemistry.
The results of this process are so precise that they are able to identify the elements needed to formulate a tailor-made sorbent with great accuracy. No model can truly replace empirical testing, but the program decreases excessive testing. It also demonstrates and predicts the effects of the selected packaging and its incorporated sorbents on the internal packaging environment.
In the IVD and medical device markets, the sorbents used are available in three different configurations: drop-in, fit-in, or built-in. To determine which of these three options is best suited for the device, the device needs to be closely analyzed via the QbD service to determine the moisture and oxygen problems it will face once packaged. This process is characterized by a large amount of detailed research and collaboration. The active packaging experts along with the IVD manufacturer and their packaging, process, and equipment engineers, research chemists, design engineers, and product development teams all work together for the duration of the project. Their goal is to select the right sorbent with the correct capacity to preserve the stability of the IVD, enhance its ability to deliver clinically acceptable specimens and results, and ensure a long-term shelf life. Once this entire process is completed, the most appropriate integration solution for the IVD is then determined—it is a standard or custom-made drop-in, fit-in, or built-in sorbent device.
|Drop-in solutions consist of a traditional desiccant or oxygen-bsorbing packet or canister and sizes to fit into a device and create an onboard solution.|
Drop-in solutions are used primarily in single-use devices. These include home-test blood or urine kits for pregnancy, blood glucose, and drug abuse. These tests are discarded after one use. The drop-in sorbent, contained in secondary packaging, provides an integrated approach to moisture or oxygen management or both, and is usually delivered in a traditional desiccant packet or canister format.
Fit-in solutions include custom-made compressed or molded sorbents that are specifically manufactured into a particular size and shape to fit into the device housing. This creates an onboard solution.
Built-in sorbents are integrated into the thermoplastic structural component of the device. This approach brings multifunctional capabilities to an existing device part. It provides either oxygen or moisture protection to IVDs that are designed for frequent use.
Drop-in, fit-in, and built-in sorbents can all be intelligent, offering customized solutions with steady-state, multi-functional management of moisture, oxygen, and hydrocarbons.
If the QbD-based service is employed by the IVD manufacturer, the manufacturer’s device gains earlier entry to market, regardless of whether a sorbent is required.
It is important to realize that not every IVD device needs a sorbent to extend its stability profile. For those that do, this entire process should be seen from two important perspectives: first, as a strategic business decision, and second, as a brand enhancement strategy. From a business standpoint, IVD manufacturers will find that by using a QbD service, they will be able to reduce development time for their IVD device by six months to a year. They are also able to identify potential product challenges and make the appropriate sorbent adjustments to mitigate the threats posed by oxygen, moisture, and hydrocarbons. This saves them money because they are able to prevent product returns caused by faulty devices. They also extend the reach and stability of their supply chains and are able to venture into international territories. Finally, they can enhance the perception of their brand by creating value through device stability, accuracy, reliability, and availability.
These four factors must not be discounted. They create a significant value proposition that most IVD distributors, resellers, and users would look for as a sign of product integrity and value. Brands that are trusted, particularly in the healthcare market, are well supported because consumers know they deliver consistently. In short, patients and consumers become the clear winners because they are using an IVD device that does its job accurately.
IVD Packaging: A Dynamic Field
The active packaging market for IVD devices is both dynamic and fast moving with new solutions being developed all the time. One of the key drivers for the development of new IVD devices is the advancement of medicine. As new methods of collecting samples are identified and as updated methods to analyze fluids and cellular materials are developed, new specialized packaging will be required. This on-going process puts new pressures on the packaging expert who will be required to understand the sensitivities of the new IVD devices, which will determine their packaging requirements.
Some of the new offerings include turnkey solutions in the form of sorbents, intelligent sorbents, multifunctional sorbents, and related sorbent-dispensing machinery that fits into the IVD production line. This provides a much shorter time to market. It’s a common mistake to assume that a sorbent’s function is simply to absorb excess moisture or the answer to an unstable chemical compound is to insert additional sorbents into a package. Sorbents can also be combined with high barrier packaging that is hermetically sealed and provides an integrated approach to maintaining the stability and efficacy of the IVD.
True IVD product stability can only be achieved by significantly slowing down the pathways to degradation and scavenging any volatilized impurities if required.—Adrian T. Possumato is global director, Healthcare Packaging at Multisorb Technologies Inc. (Buffalo, NY).