Characterization and Qualification of Processes

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Process development is a key factor in the development and manufacture of biologics. Processes must be developed and validated so that product specifications can be met to create a safe and effective biologic drug. Contract development and manufacturing organizations (CDMOs) offer sponsor companies the expertise to develop these processes, which then must be validated. Process validation is a necessity to be sure the manufacturing process produces the desired, safe product.

Process characterization

For cell culture processes, process validation must be performed before good manufacturing practice (GMP) batches can be produced for commercial production, according to Daniel Giroux, vice-president of Biologics Development at Abzena. Formal process characterization studies must then be performed before the process validation so that one can understand the impact of variations of product parameters from their targets. Small-scale studies are performed on a validated scale-down model, and the information obtained is then applied to large-scale production.

“You need to understand what are allowable ranges of process parameters and what will have an impact on your process or on the product quality, and those [parameters] that won’t [have an impact]. Then you define your process envelope …the combination of all these parameters, such as agitation, temperature, feed timing, feed amounts, and so on. [These are determined with] design-of-experiment approaches, because you have to measure [the variations’] impacts, both individually, as they change, but also when they change in combination,” says Giroux.

After process characterization and studies are performed and acceptable ranges established, batch records can be drafted, and validation protocols can be created, says Giroux. “And then you have to run multiple 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 on 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 acceptance criteria that you set up in your validation protocol.”

An essential part of process characterization is the establishment of critical process parameters (CPPs), according to Bob Schrock, PhD, senior director, 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 studies—and there can be literally thousands and thousands of samples, and [you have] done 12 or 15 different process characterization studies—the results are discussed with PD (process development) and MSAT (manufacturing, science, and technology) and from these, the actual CPPs can be determined,” 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 qualification] 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 process 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-characterized 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 validate 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 justify 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.”

Read the article in the Bio/Pharma Outsourcing Innovation eBook.

About the author

Susan Haigney is lead editor for BioPharm International®.

Article details

Pharmaceutical Technology®/Pharmaceutical Technology® Europe/BioPharm International®
eBook: Bio/Pharma Outsourcing Innovation 2025
February 2025
Pages: 22–24

Citation

When referring to this article, please cite it as Haigney, S. Characterization and Qualification of Processes. Pharmaceutical Technology Bio/Pharma Outsourcing Innovation eBook. February 2025.