Quality Pitfalls of Aging Facilities and Equipment

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Biopharmaceuticals should be produced in facilities that meet good manufacturing practice (GMP) requirements. Using older facilities and/or outdated equipment to manufacture biopharmaceutical products can make meeting regulatory and quality requirements difficult and may lead to drug shortages and higher operating costs (1). An increased amount of product rejections and recalls may also occur (1). Factors that contribute to these risks include damaged structures, difficult to remove mold, and a lack of a rigorous maintenance program that includes everything from walls to air vents, to pest control (1). Poor facility design, a lack of proper oversight, and inefficient space are also contributors to the risk associated with outdated facilities and/or equipment.

Facilities should be appropriate for their intended use, and companies must be sure the facility they are using to manufacture biopharmaceuticals is capable of meeting environmental requirements, such as those for particulates, graded space, and air changes, according to Kenneth LaRiviere, head of Engineering at Andelyn Biosciences. “Differential pressure is another critical parameter for operations in bioprocessing facilities,” he continues. “You must be able to maintain your pressure cascades as necessary to ensure a clean, compliant environment for your operations. Laminarity and unidirectional flow are critical if you are working in Grade A space, as well as other conditions such as temperature and humidity.”

Cleanliness is another key element in ensuring quality of biopharmaceuticals. However, in the past, facilities were not often built to be easy to clean, specifies LaRiviere. “Today’s spaces are built for cleanliness. Floors are impervious. Intersections of horizontal and vertical surfaces are coved. Cleaning is critically important. If you can’t clean your facility, you really can’t operate,” he says.

Risks and quality concerns

Outdated equipment and aging facilities present a variety of risks and quality concerns. Using damaged equipment can cause environmental contamination, product defects, and shutdown of operations (1). Damaged or leaking restricted access barrier system (RABS) or isolator gloves also 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 filters are in can crack and develop leaks. “That’s just something that happens with age, and something [that] would need to [be] maintained. And older fans have difficulty moving the required amount of air,” he says.

Cleanroom certification may fail if there is a lack of maintenance. “We certify our HEPA filters, but if we don’t maintain the HEPA filter housing, that can lead to failures by allowing particulate to come into the room and then [drive] particulate numbers up and [take] you out of compliance,” LaRiviere stresses. These kinds of failures, especially in critical operations such as filling lines, can lead to product recalls. “You certainly do not want to issue a voluntary product recall because you could not maintain your facility, and then that certainly would lead to more interactions with the FDA, inspections, and potential form [FDA] 483s,” he says.

Room size, and the size of the equipment in the room, can also impact quality. The facility 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 locks between graded spaces that new facilities have, asserts LaRiviere. Moving from one grade area to another may require additional gowning, which requires space for personnel to put on the necessary garments.

Read the article in the Manufacturing and Facilities eBook.

About the author

Susan Haigney is lead editor for BioPharm International®.

Article details

BioPharm International®
eBook: Manufacturing and Facilities
November 2024
Pages: 18–20

Citation

When referring to this article, please cite it as Haigney, S. Quality Pitfalls of Aging Facilities and Equipment. BioPharm International Manufacturing and Facilities eBook. 2024 November.