Factors influencing reagent blister manufacturing costs

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“Cost” is an awfully big word for being only four letters.

And as developers of point-of-care diagnostic reagent blisters know well, the costs to bring reagent blister products to market have many different sources.

Some are easier to spot than others. Some stay hidden until it’s too late, putting years of work (and lots of money) in jeopardy.

Here, we offer our take on manufacturing cost drivers and share ways a manufacturing partnership can keep your program on track for successful commercialization.

Reagent blisters of various shapes and sizes

Reagent type

The characteristics of the reagent held within a blister will impact material and manufacturing decisions that influence overall cost in two main ways.

First, some reagents are corrosive to the plastic lining of material layers that are welded together to form blisters. The corrosive effect can degrade the seal over time, increasing the risk of a leak that could damage costly analyzing equipment. To combat this, materials with different barrier properties or a different heat sealing process might need to be specified.

Second, some reagents are temperature-sensitive and must be kept refrigerated. That introduces the following cost drivers:

  • It’s much more costly to ship bulk reagent in refrigerated containers
  • It’s more costly to keep reagent in refrigerated storage
  • The heat sealing process of blister manufacturing becomes much more complicated for reagents that degrade when exposed to heat

The earlier a product developer is aware of these potential issues, the more proactive they (and their manufacturing partner) can be in identifying material or manufacturing process alternatives that keep programs on track for timely, cost-effective commercialization.

Blister material set

As the applications of point-of-care testing have evolved, so have the materials available to manufacture reagent blisters.

As this variety widens, it’s critical that developers understand that cheaper is usually never better. Granted, some programs in which the cheapest materials are specified can be successful. But in our experience, that’s rare and often only coincidental.

It’s better to rely on thorough investigation and sound engineering to land on the right materials that will result in the most reliable, least risky large-scale manufacturing.

Reagent blister processing tray

Validation requirements

Depending on industry or statutory requirements, some blister products must undergo more intensive testing for validation prior to commercialization.

Manufacturing partners add value to this stage of product development because they understand how to appropriately manage product development and manufacturing timelines that account for more time-intensive validation stages.

They also understand the additional raw material requirements that must be satisfied for successful product testing (for example, the difference in cost between non-destructive and destructive testing that results in reagent loss can be significant).

Finally, they know how to develop validation processes and are familiar with the equipment required to execute them.

Seal strength and pierce force specifications

Seal strength refers to the strength of the bond formed when blister materials are welded together via heat sealing. Pierce force is the force required to cause the blister to break to access the reagent for testing.

It’s critical that a blister’s seal strength be greater than its pierce force. If a seal is weaker than the force required to puncture a blister, reagent will leak out of the blister from the failure site and potentially damage the sensitive electronics inside an analyzer.

However, material capabilities and reagent chemical properties make for a tricky tradeoff.

For one example, some materials are incapable of achieving extremely high seal strengths regardless of how the manufacturing process is tweaked. For another, even if chosen materials and an adjusted manufacturing process do achieve a given seal strength and pierce force combination, it’s all for nothing if the reagent cannot tolerate those parameters.

Developers and manufacturing partners must learn in advance whether it’s more cost effective to iterate on material specs or manufacturing processes to accommodate actuating equipment characteristics, or whether revising the actuation process will allow for the use of more established and cost-effective materials.

Manufacturing expertise from J-Pac

Any successful reagent blister product development program hinges on the combination of the right materials and the right manufacturing process to produce blisters by the million without fail.

As such, J-Pac Medical’s diagnostic reagent blister service emphasizes design for manufacturability. This solution-seeking approach guides customers toward simplified product designs that reduce complexity and variability in manufacturing. It results in a more robust and reliable production program that saves time and money.

What reagent blister product development challenges do you face? Our engineers are ready to lend their eyes and ears to help identify the right solution. Talk to one here.

The challenge of pinpointing reagent blister seal strength specifications

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The mechanical forces specified to access reagents packaged in on-board microfluidic blisters used in point-of-care diagnostic products is essential to their clinical use. But designers of these products must consider how these activation forces relate to risks inherent to the blister manufacturing process that could manifest in later clinical use.

Identifying the ideal blister pack seal strength is arguably the most important consideration. Some practical challenges must be addressed to ensure a blister development and manufacturing program is viable for mass production.

Point of care diagnostic consumable cartridge  with blisters

What is reagent blister seal strength?

A reagent blister is manufactured from polymer-lined foils that are cold-formed into shape and then heat-welded to create a perimeter seal around the blister that keeps the liquid from leaking out.

Typically, a reagent blister is activated by a mechanism within the diagnostic instrument that applies pressure to the top of the blister while a piercing mechanism punctures the bottom of the blister, enabling the reagent to flow from the blister to the microfluidic consumable. The force required to pierce and extract the reagent from the blister is termed the “activation force.”

Seal strength differs from activation force in that it is the maximum force that the blister can withstand without leaking. Seal strength refers to the strength of the bond made by heat welding the perimeter of the blister foils, which contain plastic laminate layers that bond to each other under heat and pressure. Material characteristics, blister geometry and heat seal process temperature combine to determine the strength of that bond.

In addition, the chemistry of the reagents may cause the seal to weaken over time, so it is crucial that product developers and manufacturers choose materials wisely.

Seal strength is a critical risk management metric

In general, microfluidic-based diagnostic test developers favor higher seal strengths to prevent blisters from leaking. Higher seal forces prevent blisters from leaking their reagents onto delicate test instruments, which can risk severely damaging the sensitive electronic equipment contained inside. It’s a costly problem that also invalidates the diagnostic tests the equipment is designed to perform.

However, there are costs and technical limitations to the seal strengths that can be achieved. Reliability, or process capability, is essential. Developers should partner with manufacturers during program development to conduct compressive force testing to identify the ideal design and manufacturing specs that will result in the most reliable high-volume manufacturing of these critical products.

Dome shaped pierceable diagnostic blisters

Manufacturers must manage tradeoffs

There is a tradeoff relationship between the blister activation force and the burst force that causes the perimeter seal to fail. If the force required to activate the blister is greater than the blister’s perimeter seal strength, the blister will leak. Likewise, even if the activation force is less than the seal strength, a malfunction of the piercing mechanism can cause a buildup of forces within the blister that also exceeds its seal strength. This will also cause a leak.

One of the ways product designers have historically addressed the risk of blister leaks has been to specify very high seal strengths. Likewise, designers tend to specify strong activation mechanisms to minimize the chance the blister fails to activate.

But sometimes these specifications do not account for limitations imposed by the blister materials, manufacturing process parameters and reagent chemical properties that react with the seal. There will be a unique limit to the maximum seal force that can be achieved depending on how those variables interact.

For one example, the upper limit of seal strength differs depending on foil and polymer coatings materials. Some materials might not be able to achieve a specified seal strength regardless of how manufacturing parameters are tweaked.

For another, temperature-sensitive reagents cannot tolerate prolonged exposure to high-temperature tooling responsible for welding blister material layers together.

How a device manufacturer can help

Partnership with a medical device manufacturer closes the circle for product developers by delivering a comprehensive understanding of manufacturing considerations to product development challenges.

J-Pac Medical was among the industry’s first to provide reliable manufacturing of reagent blister products. Our engineers’ expertise has been essential to identifying the fastest, most reliable and most cost-effective pathways to market for some of the most commercially successful diagnostic reagent blister products.

It’s helpful to show as well as tell, so we invite you to order a sample blister kit as you consider working with a manufacturing provider. And if you want to make our team part of your own, let’s get in touch.

7 questions you need answered to create the ideal diagnostic reagent blister

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The most obvious marker of a reagent blister product’s success is whether the test it helps perform provides fast, accurate results that guide patient care.

But clinical factors are only a small share of what ultimately determines the viability of reagent blister products. Developers might be less familiar with the design and manufacturing considerations that will establish how smoothly your products reach the marketplace.

The questions posed below are meant to help developers sharpen their understanding of those considerations earlier in the process to better leverage the expertise of reagent blister manufacturing partners.

Liquid blisters

What are your reagent’s chemical properties?

In  general, reagent blisters are made of foil layers backed by a polymer film which are welded together. Because different reagents have different chemical properties, they don’t always play nicely with blister materials.

Prior consultation with a manufacturer is essential to ensure that volatile, corrosive or degassed reagents are paired with materials that will not degrade in contact with the reagent over time.

J-Pac has developed a widely used reagent blister material set that has provided sufficient chemical resistance for the majority of our reagent blister customer applications. If that primary set won’t work, our team will then identify the ideal alternative materials that will yield better results.

Is your actuating force adequate for your blister design?

Two forces are required to successfully dispense reagents from blisters. The first is a one-time force required to puncture the blister. The second is a persistent force required to expel the reagent.

Obviously, an actuator must be strong enough to pierce a blister. But it also must be able to achieve the force required to continue expelling the reagent into the microfluidic consumable.

But the puncture force cannot be so strong that it overcomes the seal force created when blister layers were welded together. If the welded seal fails, reagent will escape into areas it’s not meant to go. This would invalidate a test and likely damage costly analyzing equipment.

Manufacturing partners are essential to choreographing the dance between blister design, manufacturing considerations and their relationship to actuating equipment.

Multiple dome shaped piercable reagent blisters

Have you accounted for reagent loss?

Once a blister is pierced, reagent is lost in transit from the blister to the analysis site.

Some reagent stays behind in the blister itself. Some remains in the reservoir below it. Some clings to the wetted surface of the microfluidic channel leading from the reservoir to its final destination.

Blisters must be designed with enough surplus reagent capacity to guarantee the appropriate amount reaches the analysis site.

What are your head space tolerances?

When a microfluidic reagent blister is filled, a meniscus is formed that prevents the blister to be 100%filled. Likewise, the film sealing process requires some fill tolerance to prevent fluid from migrating to the seal surface. J-Pac recommends designing for a blister fill volume of 80%, meaning the actual blister is larger than the amount of fluid dispensed. Many customers use the design of the microfluidic cards to handle gasses. If head space cannot be tolerated, J-Pac can provide a 100% fill through an alternate process that designers should recognize that is a slight premium to the conventional approach.

Head space is also related to the need for degassing as the gas within the head space will react with the reagent. This is common for mineral oil applications, for example. J-Pac can address this issue through its degassing and vacuum sealing process.

Do you require refrigerated storage?

Keeping reagents cool for the duration of their lifecycle introduces added storage, logistics and manufacturing concerns that drive up production costs.

Consider the lifecycle of a reagent formula:

  • It is blended in a manufacturing facility under refrigerated conditions
  • It must be kept in cold storage prior to shipping
  • It can only be shipped via refrigerated truck or air freight and not in bulk shipping containers
  • It must remain in cold storage prior to manufacturing
  • Heat sealing during blister manufacturing introduces the risk that reagents reach too high a temperature
  • Finished testing cartridges must stay in refrigerated storage until use

Developers must be fully aware of the added cost and difficulties that come with temperature-sensitive application.

What is your scale-up plan over time?

The way you plan to scale up production is an important manufacturing and cost consideration.

Will you only produce at low volumes of around tens of thousands of units to a few hundred thousand units per year? Will you scale up to mid-volume production of several hundred thousand units to a couple million annually? Will you achieve high-volume production of tens of millions of units or more?

Each volume differs in the capital required to secure supplies and equipment and the cost to manufacture each unit. Obviously, costs decrease as scale increases. Developers should be prepared for lower returns—or even losses—in early production stages. Gains at higher volumes will erase early losses.

Can your design leverage the J-Pac blister platform?

Because J-Pac Medical was among the first to develop reagent blister manufacturing technology, we’ve created a proven platform that’s brought tens of millions of reagent blisters to market.

Adopting a proven platform comes with three key advantages:

First, this eliminates most of the blister design and manufacturing process legwork, speeding the development timeline significantly.

Second, an existing platform means material procurement channels are already established. In addition to further speeding your program, this results in lower material costs.

Finally, a proven platform means our manufacturing infrastructure is already geared up to produce at any volume you require; the equipment and labor force responsible for manufacturing is already in place. Again, this reduces overall cost.

To learn whether the J-Pac diagnostic reagent blister platform will work for your product, order a sample kit now. We might be about to lift a great weight off your shoulders.

Get more guidance on reagent blister manufacturing

J-Pac Medical has been on the forefront of microfluidic testing products and processes ever since the technology began to emerge over two decades ago. For more detailed product planning information, read our reagent blister design development white paper.

And, our engineers would love to hear more about how your product planning is coming so far. To ask questions or brainstorm ideas with one of them, reach out here.