Challenges And Solutions In Aseptic Evolution
By Katie Anderson, Chief Editor, Pharmaceutical Online
Aseptic processing has undergone a considerable evolution over the past 35 years in new equipment, standards, procedures, training and regulation. Navigating these challenges is essential to minimizing risk, and I had the pleasure of attending a panel at ISPE’s Aseptic Conference on March 24, 2026, that highlighted the demands facing aseptic processing and potential solutions moving forward.
The panel featured Oscar Perez Villatoro (Integrated Project Services), Christa Myers (CRB), Dennis West (INCOG), Norman Nicklaus (Amgen), Jörg Zimmermann (Vetter Pharma), Ryan Waldhart (Grand River Aseptic Mfg Inc.), and was moderated by Paul Valerio (Integrated Project Services).
Challenge: Cross-function Understanding
Being a subject matter expert in aseptic processing is challenging enough, but communicating that understanding to other industry partners adds an extra hurdle.
As Myers pointed out, when barrier systems were first used, the industry questioned how they would educate on the process. She referenced industry veteran Jack Lysfjord, Ph.D., who once commented, “how are we going to get the FDA to understand all of this.” It is repeating itself, according to Myers.
“How are we going to get our manufacturers, agencies and design firms to understand all of this. We have some stable systems out there, and they have been stable for years. Are we doing things that are actually going to make a change?” added Myers.
She continued that it is up to us in the industry to know and manage our risk. “We need to know our data to show that what we are doing is not a problem. When you do see problems, we have to start digging to the root cause to make sure we are managing risk. We have to be responsible for that,” she noted.
Challenge: Breaking First Air
Though sterile filling lines are quite advanced in today’s environment, that wasn’t always the case. Therefore, Valerio asked the panelists if there could be a risk-based rationale for breaking first air with a non-sterilized object.
To this, Nicklaus responded that he would try to engineer that out if he could. “We would avoid that as much as we can. There would have to be a risk around that, or you would have to do some additional monitoring around that,” he explained.
Myers furthered that they used to say that bad design doesn’t justify bad practices, but she also noted that “at the time, it was not bad design, and they are managing their risk.” “There are a lot of lines out there that are in place that look similar to that, and they are all having to ask these questions right now,” Myers continued.
Challenge: Bracketing Opposition
Bracketing is still accepted by the FDA and EMA, but recent enforcement has shown a tightening of the belt for validation. Valerio poised the question to panelists on the direction of eliminating the ability to bracket.
Waldhart presented the perspective of a CDMO, where eliminating the ability to bracket would be compounded. His team has years of data with different syringe sizes, container sizes, tubing sizes, fill needle sizes, etc., all represented within their media fill programs, performed in triplicate. “What we are seeing from our clients is the push to have one batch fully representative of their product, so they can grab one summary report and use that for the submission. The bigger impact is the line time,” he explained.
Additional media fills for validation affects the bottom line and ultimately the cost of the final drug, noted Villatoro. “I want to put focus on the cost of good manufacture. Twenty-two additional media fills means there is downtime, and the company needs to recover. That all goes to the cost of the goods. That all goes to the cost of the final product, and is that helping their patient?” added Villatoro.
Challenge: New Technology
Reducing human intervention often means the introduction of technological innovations such as isolators, robots and settle plate changers. Just because a technology is novel and available, though does not mean that it is suitable for a line.
Villatoro cautioned attendees to approach technology with baby steps, with caution, and with data. While he has seen technology that reduces intervention and is easy to adapt, he sees others that are more difficult. “The gloveless isolator is only as good as how many batches you lose. If your product is extremely expensive, how many batches are you willing to lose as a result of an intervention? Does it have to be a new innovation to reduce intervention? Single use systems were available in 2012. We were reluctant to use them, but now they are standard technology. It is stepping stones,” explained Villatoro.
West recommended sitting down and discussing technology issues. “The real opportunity is when we sit down and we discuss what is really important and what is nice to have,” he added.
Challenge: Operator Training
It is about the culture you create for the operators, noted Nicklaus. “You need to have a culture that is both technical and performance-driven with your operators that use your technology,” he explained.
All of the panelists agreed—training for operators needs to be comprehensive, frequent, and interactive. “Training has changed to be more like a video game. Companies are going to need to stay on top of the cutting edge of those training methodologies, so it isn’t a boring, dead tape that no one listens to,” she explained. And the operators need to stick with it to understand the why. “It takes a significant amount of rigor to understand the why behind what makes that box magical,” she continued.
ISPE is coming out with a good practice guide for smoke studies, noted Waldhart. “One of the major highlights is using it as a tool for training purposes. If we are doing the work already, let’s implement it in a training program,” he added.
Reviewing training videos frequently is vital, according to Nicklaus. His team reviews them with the operators on a regular basis to make sure they match their processes exactly. “Our expectation is the videos are aligned 100% with what is happening on the floor.”
Myers recommends building SMEs into everything. “Train SMEs in everything, from gloves, to isolators, and beyond, that understand the basics of what is going on,” she added.
Challenge: Transferring Knowledge
Collaboration between teams is not only helpful when operating a successful sterile drug line, but it is vital.
Zimmerman recommends getting operators, engineers, and quality involved early in purchasing a line to set them up for success. “If you just hand it over, something will go wrong. We want them involved and for them to have a say in it as well. Build it in a way that it can be operated. You have to set them up for success and not for failure both with how the machines are run and how the procedures are written,” he recommended.
Similarly, it is invaluable for aseptic manufacturers and machine builders to collaborate to ensure the results are as expected. West explained, “The precision that comes out of these machine builders is astounding, but there was a gap in aseptic understanding in the past. Manufacturers have an enhanced understanding of aseptic, but our machine building expertise may be limited. It is really when we come together, that we both end up learning. That move has been in a positive direction, bringing us both to a better place.”