By Mitch Gonzales, AES Clean Technology, and Brian Weed, Controlled Contamination Services
Overlooking a cleaning and disinfection scheme as part of a biopharmaceutical manufacturing facility’s design and construction is an all-too-common misstep in effective cleanroom design and operation.
Between 2015 and 2019, FDA industry compliance requirements for cleaning, sanitization, and maintenance under section 21 CFR 211.671 yielded a total of 381 FDA citations (i.e., Form 483 Inspectional Observations). In 2019 alone, 99 observations were issued, elevating “equipment cleaning and maintenance” to the fifth-most prevalent type of citation issued by FDA that year.
Contamination control (21CFR 606.145.a)2 also represents a high-incidence FDA observation category. The FDA provides specific guidance3 for cross-contamination control in product license applications, requesting a narrative description of the procedures and/or facility design features for cross-contamination control and containment.
Still, biopharmaceutical firms contracting out cleanroom design and construction services often focus only on core, process-specific facility attributes, underestimating the importance of an integrated cleaning and disinfection strategy. Or those firms consider cleaning and disinfection strategy the realm of whomever is contracted to handle such maintenance later.
While this dynamic frequently is true, decisions made during cleanroom design — based on considerations of multiproduct use, processing steps, operational flows, and the challenge of cleaning particular structures or surfaces — greatly impact a facility’s start-up and long-term operational cost. These decisions also can shape the ease of facility expansion while minimizing the risk of construction contamination due to ongoing GMP production operations.
In this article, we examine how cleanroom design and construction techniques, as well as construction materials, impact the cleaning and disinfection of classified areas. Also discussed are critical factors influencing the schedule, quality, and lifecycle cost of a newly constructed biomanufacturing facility.