My initial exposure to sterile product manufacturing was in 1973 when I first observed the aseptic filling of small-volume parenterals. The reader is likely quite familiar with the image: aseptically garbed operators wearing face masks, goggles, and sterile gloves separated from a filling line covered by HEPA filters by flexible curtains. That was state-of-the-art aseptic processing 50 years ago. The aseptic area had been built in the mid-1950s! Yet in 2024, the same scene can be found in hundreds, if not thousands, of facilities worldwide. Something is wrong here – my television is 4K, my cell phone works anywhere in the world, my car is smarter than I am, and technology has made countless changes in everyday items. Yet, we still manufacture sterile products as we did decades ago. My good friend, Hal Baseman, past PDA Chair, has said much the same, “My aseptic processing career started in 1978. If I were asked then to predict what aseptic processing would be like 45 years in the future, I could not have guessed what it would become. That is because not much has changed. We still do things pretty much as we did back then. What other ‘science-based’ industry can make such a dubious claim?”
It’s hard to understand why when everything else is so very different and improved, there’s only been a modest shift in sterile product manufacturing. While many major firms have invested in advanced technologies, there’s a host of smaller firms unwilling or unable to do so. At the same time, it’s important to understand that our industry is very much an outlier with respect to progress. The dairy industry produces vast quantities of products aseptically using technologies substantially more advanced than what you might find in a pharmaceutical plant. The available systems can hardly be APR_SeptOct2024.indd 26 10/3/24 2:53 PM considered novel, the first pharmaceutical isolators came into use in the early 1980s. Around that time, Jim Akers, past PDA chair remarked to me as we walked through the PDA exhibit hall, “We’ve just seen the future of aseptic processing. It’s going to change everything.” Not long afterward I boldly predicted that in 15-20 years, manned cleanrooms for aseptic processing would no longer be constructed. The presence of “Pigpen” in aseptic cleanrooms was something we needed to eliminate.
Where did it all go wrong? I think the answer lies in unwarranted expectations for perfection. My essay “Paradise Lost” decries the missteps that crippled the acceptance of isolation technology.1
- “It has to be sterilized” – something that manned cleanrooms will never be …
- “It can’t leak” – even though cleanrooms must …
- “It requires laminar airflow” – to sweep away contaminants from personnel that aren’t inside …
The list of excuses goes on and on, along with the inevitable foot-dragging that has kept aseptic processing mired in the past. Perfect has proven to be the enemy of better. Attempts to provoke greater regulatory pressure have met with limited success. While the FDA has openly voiced its preference for isolation technology over less capable approaches, EMA has proven more reticent. The recent Annex 1 revision is ambiguous, drawing heavily on cleanroom practices poorly suited to a very different technology. Its support for meaningful improvement in aseptic methodologies is underwhelming.
Isolation technology is merely the next step in sterile product manufacturing. There is still more potential ahead – closed systems, increased robotics, machine-based systems rather than environmental ones, etc.
“Don’t stop thinking about tomorrow
Don’t stop, it’ll soon be here
It’ll be better than before
Yesterday’s gone, yesterday’s gone.2
References
- Agalloco, J., “Paradise Lost: Misdirection in the Implementation of Isolation Technology”, Pharmaceutical Manufacturing, Volume 15, No. 4, p. 34, 2016. Continued online at Pharmmanufacturing.com. Reprinted in Aseptic Processing Trends eBook, pp 9-17, July 2017.
- Don’t Stop Thinking About Tomorrow (Christine McVeigh, Fleetwood Mac, 1977)
Author Details
James Agalloco- Agalloco & Associates
Publication Details
This article appeared in American Pharmaceutical Review: Vol. 27, No. 6Sept/Oct 2024Pages: 26-27
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