Datwyler testing evolves as health care regulations change

FAIRLAWN, Ohio—In industries where the goal posts are moving at a breathtaking pace—from the sweeping move toward electrification and sustainability to the packaging integrity of COVID vaccines—ripple effects can be felt in just about every related industry.

That includes the regulatory space, where companies like Altdorf, Switzerland-based Datwyler have to remain current with the pace of change, and then adapt to it.

And that is not easy, as speed-to-market continues to be a high priority for both the medical component manufacturer and the patient.

"We are engineering materials for a more sustainable world, and it is in this world where we need to have ideas come to fruition," said Roman Ventura, material applications manager at Datwyler Pharma Packaging in Middletown, Del. "We need to continue to bring value to our customers. And that is why I am excited to talk to you about robust testing."

Ventura spoke as part of the first day of the Healthcare Elastomers Conference, which took place May 8-9 in Fairlawn.

Datwyler Pharma Packaging manufactures elastomer components for injectable pharmaceutical packaging like syringes, stoppers, caps for vials, as well as rubber components for cartridges like those found in epinephrine injection pens.

Specifically, Ventura works in the health care solutions and industrial products divisions.

Datwyler, with about 2,870 employees, provides more than 20 billion components to these industries every year, as Datwyler also maintains a presence in Central and South America, Europe, India and China.

"That's why we say, 'the sun never sets on Datwyler,' " Ventura said. "We make a lot of the elastomers used in health care applications. Hopeully, you will see components with a lot of manufacturing and engineering going into them—but that all of that is not noticeable."

Ventura added that "material expertise is part of Datwyler's core competencies."

"With 100 years of experience, we have the ability to do in-house research and development and the testing of the life cycles of those materials," he said. "We have decades of knowledge that assist in this."

Chemical compliance can be a robust process, one that requires a proactive stance in managing substances of concern—including PFAS and other materials.

"What we are talking about here is package integrity and the absence of risk," Ventura said. "At the end of the day, this means customers are focusing on integrity, through the absence of risk, that there are any contamination issues."

As the EU updates its Annex 1 regulations—supplementary guidelines to the EC-Good Manufacturing Practices Guide, with specific requirements for the production of sterile medicinal products—it is calling for CCI (Charlson Comorbidity Index)-validated methods.

"And this has an increased focus on regulatory scrutiny coming with it," Ventura said. "We are seeing the same thing with the FDA ... in finding what is suitable to maintain seal integrity."

As such, there has been a shift in testing methods for syringes, stoppers and plungers, from probability-based methods to deterministic methods, Ventura said.

"Overall, this also shows a shift in focus to elastomeric technology," Ventura said.

For instance, U.S. Pharmacopeia Chapter 382 now includes "the whole nine yards," as Ventura put it, on seal integrity.

This is important to note, he said, as it demonstrates a move away from sterility testing and toward package integrity testing.

"The main thing is no longer sterility preservation, but a focus on integrity and testing," Ventura said. "We want to ensure that the rubber materials are producing a seal that does not have leakages above the limit where we know (it) will have detrimental effects."

The generally accepted Kirsch Criterion, a helium-based, deterministic method that Datwyler uses to measure contamination, can detect "microbial ingress" down to .2 microns.

Essentially, Ventura said, deterministic risk considers the impact of a single risk scenario, whereas probabilistic risk considers all possible scenarios, their likelihood and associated impacts.

In deterministic testing, there is a correct and an incorrect answer, whereas probabilistic testing is based on what is supported with existing evidence.

For instance, if the weather forecast calls for a 70-percent chance of rain, is it correct if it does rain, or incorrect if it does not?

The answer, according to Dataspire, a science literacy website, is neither, as the forecast is based on the probability of rain.

"Both have principles that are qualitative and quantitative," Ventura said. "When judgment is done by the operators of the device, this is probabilistic ... and we are trying to get to deterministic (testing).

"Container closure system integrity is key."

A second deterministic test involves a laser diode that fires through a vial to determine aging and cold storage use for all life cycle phases, Ventura said.

This particular test can measure microbial ingress and leakage levels down to .01 microns.

"And that is pretty low," Ventura said.

For its part, Datwyler specializes in helium detection, where He is the tracer gas that is used for incredibly sensitive leak detection.

"This is for high sensitivity, where you have your tracer gas inside the vial itself," Ventura said. "It is then sent through a very fast pump to a mass spectrometer, which detects the rate of leakage."

The downside to this form of testing, Ventura said, is that it must be performed offline, or outside of the manufacturing process.

Datwyler offers helium testing at its Middletown site, and uses some of the other testing protocols at a site in Belgium, measuring capping and plunging conditions.

In using for helium testing for leakage rates, He has to get into the vial one way or another.

Holes can be punched in the stopper to get the He in, however that can allow other contaminants and variables to enter.

Following a case study, Datwyler now uses a style that gets the He in via holes in the glass vial, knowing that "we can seal the glass with a sticker."

"We finally found one that works the best," Ventura said. "We found a way that is not through stopper holes or through melting a hole in the stopper to determine leak rates."

Another "orthagonal" form of testing, or statistically independent method that can be done during production, is residual seal force testing, Ventura said.

"Helium needs to be done offline, but this you can do online," he said. "What are your capping conditions? When you have good crimping conditions and good RSF values, you now have proof to give to your customers (who are) going through the manufacturing process."

RSF helps to measure "break loose force," which occurs when the plunger in the syringe has pressure applied and starts moving; and gliding force profiles, which can be gleaned when the medicine is extruded as the plunger is moving.

"A registered nurse might have to apply a lot of force to get the plunger to start moving," Ventura said. "Would you want a doctor or nurse to be pushing really hard on it?

"I know I wouldn't."

An inconsistent and "jerky" plunger also is bad news.

"If that is your kid, that kid is going to be crying with that pressure and inconsistency," Ventura said. "There is a reason why we need to ensure the properties are well-maintained. We are looking for meaningful, quantitative acceptance criteria.

"No one wants their loved ones having an issue."

Ventura cautioned that the U.S. Pharmacopeia now has no official, meaningful acceptance criteria that designates a single testing method for all package and product delivery systems.

"They have no method that they can say should be used across the board," Ventura said. "And it is because all applications are different (for the thigh, arm or mouth, for instance) that the end product developer has to be able to determine what those acceptance criteria are."

And to complicate things further, test force and test speed are subject to agreement.

"One test can be successful while another can fail, like the blue dye test can show 'pass' while the He test could show 'fail,' " he said. "And vice versa.

"In closing, there is a shift toward deterministic techniques because the integrity evaluations—as recommended by the official guidance and regulations—are leaning toward making sure there is a validated program. The end user is responsible for establishing the criteria with the manufacturer, and you have to think about all the parts you have to worry about (validating) to be able to do that particular test."

Rubber News wants to hear from its readers. If you want to express your opinion on a story or issue, email your letter to Editor Bruce Meyer at [email protected].

Please enter a valid email address.

Please enter your email address.

Please verify captcha.

Please select at least one newsletter to subscribe.

View the discussion thread.