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www.biopharminternational.com Manufacturing and Facilities eBook November 2024 BioPharm International ® 19 Facilities Risks and quality concerns Outdated equipment and aging facilities present a variet y of risks and qualit y concerns. Using dam- aged equ ipment ca n cau se env i ron ment a l con- tamination, product defects, and shutdown of op- erations (1). Damaged or leaking restricted access barrier system (R ABS) or isolator gloves a lso can put product at risk. Particulates can be problematic in older facilities, according to LaRiviere, not necessarily because the HEPA filters fail, but because the housings that the f ilters are in can crack and develop leaks. "That's just something that happens with age, and some- t h ing [t hat] would need to [be] ma inta ined. And older f a n s h ave d i f f ic u lt y mov i ng t he requ i red amount of air," he says. Cleanroom certification may fail if there is a lack of maintenance. "We certif y our HEPA filters, but if we don't maintain the HEPA filter housing, that can lead to failures by allowing particulate to come i nto t he room a nd t hen [d r ive] pa r t ic u late num- bers up and [take] you out of compliance," LaRiv- iere stresses. These kinds of failures, especially in cr it ica l operat ions such as f i l ling lines, ca n lead to product reca l ls. "You cer ta in ly do not wa nt to issue a voluntar y product recall because you could not maintain your facility, and then that certainly would lead to more interactions with the FDA, in- spections, and potential form [FDA] 483s," he says. Room size, and the size of the equipment in the room, can a lso impact qua lit y. The facilit y needs to be "fit for purpose", according to LaRiviere. "I've seen facilities that have been repurposed, and they put a large bioreactor into the room. It just doesn't fit really well. You can get it in, but it just doesn't fit. So, it makes it difficult for the operators to do what they need to do correctly," he says. In addition, older facilities may not have the air lock s bet ween g raded spaces t hat new faci l it ies have, a sser t s L a R iv iere. Mov i ng f rom one g rade area to another may require additional gowning, wh ich requires space for person nel to put on t he necessar y garments. Ensuring facilities meet those expectations Identif ying and mitigating risks associated wit h older facilities and/or outdated equipment is im- perative. T here should be a com m itment to keep resources updated. "Strategic planning ensures baseline resource al- location for routine upkeep and maintenance as well as top priorities for each site captured in their annual Quality Plans," said Nicholas Violand, director, Enter- prise Regulatory Compliance, Johnson & Johnson in a presentation at the 2024 PDA/FDA Joint Regulatory Conference (1). Site monitoring programs should be established to identify risk including shop f loor oversight by the quality department; internal, external, and corporate audits; and regulatory inspections (1). Any potential risks should be documented and communicated in the quality system so that corrective actions can be made. "Processes should be developed to categorize findings into relevant quality system areas and rank risk," according to Violand (1). Data analytics should be used to identif y product impacts and corrective action plans need to be robust (1). Upg rad i ng to adv a nced tec h nolog y m ay help ensure qua l it y cont rol, a nd t hese new tech nolo- gies may require less manufacturing space and re- duce t he need for additiona l resources (1). "Some high-volume products may benefit from investment in newer, more efficient platforms such as continu- ous manufacturing," said Violand. When it comes to equipment, a good business de- cision may be to have backups ready to go if utility equipment fail, remarks LaRiviere. "I don't have to spend a whole lot of time doing predictive mainte- nance activities, because if it fails, the system au- tomatically switches over to the online spare, and there's no issue." However, equipment that operates in a harsher environment, such as boilers and steam generators should be inspected reg ularly and re- placed after some time, warns LaRiviere. The fact that times have changed should also be taken into consideration when assessing an older facility or equipment. "Expectations have changed over the years. [A] piece of equipment that might have been considered state of the art 10 years ago is no longer," says LaRiviere. Fixed bioprocessing equipment such as bioreactors were primarily used 10–15 years ago, but currently single-use equipment is more widely used. "I'm aware of up to 6000 L ca- pacity for single-use equipment for bioreactors. It's a great option if your process allows that, but when you get into those bigger volumes, fixed stainless-steel equipment is typical," he adds. BioPharm International® spoke with Kenneth LaRiviere, head of Engineering at Andelyn Biosciences, about how manufacturing biopharmaceuticals in an aging facility might cause regulatory and production problems. He also discusses what companies can do to be sure they are meeting good manufacturing practice standards. Scan the QR code to watch the entire interview. https://www.pharmtech.com/view/ pitfalls-in-aging-facilities