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Bio/Pharma Outsourcing Innovation February 2025 BioPharm International ® | Pharmaceutical Technology ® 23 cords can be drafted, and validation protocols can be created, says Giroux. "And then you have to run mul- tiple at-scale batches, so you know if your commercial process is going to be at the 2000-L scale, then your validation protocol will dictate how many batches you want to run. A typical number is three. It doesn't have to be three. It could be more. Possibly could be less, rarely," Giroux explains. "And then you execute your production batches, and you analyze heavily the impact of the product that's coming out. You do more analysis than you normally would, something like this, and then you basically show that you met the criteria that you set up in your validation protocol." An essential part of process characterization is t he establishment of critica l process parameters (CPPs), according to Bob Schrock, PhD, senior direc- tor, Global Head of Process Development, at Lonza. Proposed critical process parameters (PCPPs) are obtained after process characterization studies are carried out. "Once we do all the process characterization stud- ies—and there can be literally thousands and thou- sands of samples, and [you have] done 12 or 15 differ- ent process characterization studies—the results are discussed with PD (process development) and MSAT (manufacturing, science, and technology) and from t hese, t he ac t ua l CPPs ca n be deter m i ned," says Schrock. "These CPPs are integrated into the process, and the validation of the process is then basically what we call the PPQ [process performance qualifi- cation] runs, the PPQ runs that are done just prior to commercialization. For [much of the] processes, the cell culture portion is only part of the process, for example, [with] viral vector manufacturing. There's, of course, purification steps downstream from the [cell] culture portion." According to Schrock, PPQ runs show that a pro- cess is validated and robust and the number of runs needed depends on the variability of the process. "For a viral vector program that uses a large and well-char- acterized cell bank, you can do the minimum of three runs if they run perfectly. But for something [such as] autologous cell therapy, where you are starting with different cells from patients or healthy donors, you may need to do more," says Schrock. "And then, of course, the question of using healthy donors to val- idate a process that is intended to start with patient samples and patient leukopaks packs, that's always a deep and spirited discussion where you need to get creative on how you justif y that. But at the end of your PPQ runs, you write a huge report that's part of your BLA [biologics license application] submission, and it's a cornerstone of your BLA. [It] proves that your process is validated." Analytical tools Process characterization studies may be performed by tools such as failure mode and effects analysis (F M E A) accord i ng to Sch rock. F M E A pr ior it i zes risks and provides risk mitigation options, explains Schrock. The t y pes of studies that need to be per- formed can then be established. "We will typically start with a workshop with sub- ject matter experts from process development, an- PROCESS DE VELOPMENT Optimizing Process Development for Microbial Fermentation BioPharm International® spoke with Paul Mugford, direc tor, Biologic s Process Development at BIOVECTRA, to find out what approaches works best for optimizing processes in microbial fermentation. Watch Now! https://www.biopharminternational.com/view/optimizing- process-development-for-microbial-fermentation Optimizing Process Development for Biologics Watch the full interview with Daniel Giroux, VP of Biologics Development at Abzena, in which he discusses approaches for optimizing process development for the production of proteins . Watch Now! https://www.biopharminternational.com/view/ optimizing-process-development-for-biologics