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Preventing contamination requires quality systems to be in place, including routine cleaning, a robust cleaning validation program, and preventive maintenance.
The Benjamin Franklin axiom, “An ounce of prevention is worth a pound of cure,” holds true for cleaning of pharmaceutical manufacturing lines and is one of the ways to build quality into drug products. Not enough companies focus on preventive measures, however, as evidenced by the high number of FDA 483 observations related to cleaning, sterilization, or a lack of appropriate procedures, noted Shabana Chaudhry, an aseptic trainer at Allergan, in a presentation at the CBI Institute of Validation Technology Network’s conference on Cleaning Validation and Critical Cleaning Processes (Aug. 18–20, 2015).
Also at the conference, Jeanne Moldenhauer, president of Excellent Pharma Consulting, discussed the need for a paradigm change to preventing contamination problems rather than merely reacting to them. "A 2011 study (1) indicated that the cost for the pharma industry to do reactionary control mechanisms is 10 times higher than if the company prevented the contamination from happening," Moldenhauer told Pharmaceutical Technology. "Unfortunately, few companies have widely implemented preventative measures."
Prevention, said Moldenhauer, includes actions such as routine cleaning and disinfection, but can go beyond that using technology available today, such as a mold barrier to prevent mold growth. As another example, she explained, "A gowning room used a paint that prevented microbial growth and resulted in extremely low counts even though there would be a high number of bacteria present during the initial gowning process (coming in from outside in street clothes)."
Cleaning and cleaning validation best practices
Having a robust cleaning validation program is another key to preventing contamination problems. Beth Kroeger, technical services manager at STERIS Life Sciences, spoke at the conference about how to ensure a successful validation. “When you make a validation plan, it is crucial to understand the manufacturing process and the manufacturing and cleaning equipment, as well as the role of the equipment in the process,” Kroeger explained to Pharmaceutical Technology. "The process lifecycle approach calls for having this understanding up-front."
She explained the importance of having all the involved departments-including quality, process engineering, and manufacturing-work together to identify and prevent potential problems even before making the validation plan. For example, a piece of equipment may have a difficult-to-clean section, such as an air-liquid interface, baffles, or vortex breakers. "You need to be aware of this equipment design so you can have the correct cleaning procedures in place," said Kroeger.
Although in many cases, process engineers must work with existing equipment (whether or not it is easily cleaned), it is ideal to involve all departments when initially specifying equipment and to consider the cleaning processes as part of this specification, added Kroeger.
Periodic maintenance of tanks and clean-in-place equipment is a crucial preventive measure to ensure that tanks are passive and reduce risk for rouge buildup. "Rings in buffer tanks is a hot-button issue that has recently been noted by FDA," said Kroeger. "Although these tanks are typically cleaned with water, a best practice is to implement a periodic cleaning (once a month or once a quarter) with alkaline detergent."
Another best practice is designing a cleaning process by using coupon studies to look at residues and do a risk analysis for soils. "What you think is the hardest to clean residue may not be, but a coupon study may help identify this," noted Kroeger.
Quality systems prevent contamination
Preventing contamination requires quality systems to be in place and functioning properly, noted Chaudhry. These include proper facility design, a cleaning and disinfection program, clear and detailed standard operating procedures, and personnel training. At the conference, Chaudhry described common sources of contamination, which are predominantly human-borne but include some that are routinely overlooked, such as the water system, parts washer, new equipment, cleaning equipment, incubators, and others. In addition to controls and cleaning-and not missing these overlooked areas-maintenance, validation, environmental monitoring, and quality unit oversight are crucial, said Chaudhry. "If any part of the quality system is not in control, the facility is not in control and the risk for contamination increases," she explained. With effort and attention, however, it is possible to have control over processes and thus better prevent contamination.
1. J. Macher, “Business Case for Quality,” presentation at the Pharmaceutical Quality Systems (ICH Q10) Conference (Arlington, VA, Oct. 2011).