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16 Pharmaceutical Technology ® Trends in Manufacturing eBook May 2024 PharmTech.com MULTIMODAL FIGURES ARE COURTESY OF THE AUTHOR. would be introduced, including unidirectional f lows and segregated manufacturing areas. • Viral vectors. Viral vectors are highly leveraged for the deliver y of "genetic payloads" in CGT manufacturing. A viral vector is essentially a stripped-down virus that retains the ability to enter into cells and deliver the genetic payload. The introduction of a virus poses enhanced con- tainment requirements, of ten mirroring the viral clearance activities for mAbs. The facility design must account for this increased contam- ination risk. • LNPs . L N Ps a re ut i l i zed i n m R NA del iver y, where t hey stabi lize a nd protect t he m R NA. Given t heir sy nerg y, stabi lit y, a nd at t r ibute alignment, the segregation strateg y of the fa- cility design would be the same in terms segre- gation and f lows. • Oligonucleotides. Oligonucloeotides (oligos) are a class of ATMPs that are used in gene and pro- tein expression. There are a number of manufac- turing challenges around oligo manufacturing. One is the use of solvents in the manufacturing process, which results in a higher level of hazard- ous process waste that must also be addressed. Given the safety concerns associated with sol- vents, the segregation strategy must provide a solution for managing f lammables and solvents. HVAC design/area classification For a growing number of ATMP facilities in the CGT space, a key challenge is pinpointing risk mitigation strategies that target contamination control. A direct outcome of these efforts is the potential reduction of area classifications within the manufacturing spaces, consequently simplifying the segregation strategy and optimizing the overall heating, ventilation, and air conditioning (HVAC) system design. T he com mon ly used H VAC con f ig u rat ions for ATMP products are three basic alternatives applica- ble to cell therapy, vector manufacturing, and related cell culture-based products. These alternatives are primary/secondary using air handling uni/fan coil unit-based local recirculation, primar y/secondar y using fan filter unit-based local recirculation, and primary only, with no recirculation. In a detailed design analysis on the applicability of HVAC system design for ATMPs in Grade B spaces, the study supported the use of recirculated HVAC systems. These systems were deemed appropriate and capable of meeting the defined global regula- tory expectations that have been traditionally tied to once-through air systems (6). By minimizing the HVAC design criteria and re- ducing area classifications through system design optimization, each modality can be "grouped" under a simplified classification approach: FIGURE . Illustration depicts the foundational elements of the enterprise model. SS is stainless steel. SUS is single-use system. EBR is electronic batch record. HSE is health, safety, and environment. MES is manufacturing execution system. LIMS is laboratory information management system. MRP-II is manufacturing resource planning II.