Manufacturers of cell-containing products are adopting new techniques to work around unclear regulatory guidance on particulates. That’s the experience of Diana Colleluori, PhD, principal chemistry, manufacturing and controls (CMC) consultant at Biologics Consulting.
According to Colleluori, cell-containing products can be harder to visually inspect for particulates, as they’re not clear and are often stored in opaque bags.
“Processing and testing cell-containing products already has challenges because they can’t be terminally sterilized,” she explains. “It’s also harder to make a visual assessment to meet regulatory requirements because they already contain cells and the final product is usually in a cell-freezing bag.”
The particulates are mostly (90%) plastic that enter the product from contact with the inside of single-use equipment used during manufacturing, she says, adding that other particulates can enter from product manipulation and, thus, it’s best to try to minimize this.
Companies that Colleluori has worked with have tackled this problem by running their process with the formulation buffer, but minus cells, she continues. This allows them to assess particulates in a clear solution, outside of a bag, which they can then extrapolate to running the same process with cells.
“By testing visible and sub-visible particles in those samples, you can prove your product contact materials are expected to meet the limits for your cell-containing products,” according to Colleluori.
The company can also run quality control tests on a small sample of the final product. Among the tests carried out are those based on the United States Pharmacopeia (USP) chapters 790 for visible particulates and injections,1790 for visual inspections of injections, and 788 for the sub-visible particles.
In addition, EU guidance on visual inspection of particles can also be relied upon. Which tests are run should depend on the method of administration, adds Colleluori.
“If you’re doing an intramuscular injection, it’s probably a little less rigorous than an intrathecal injection of products that have stricter regulations on the number of particles and sub-particles that can be present,” she says.
