Charles River Laboratories

Jon Kallay

Quality Control Testing of Cellular Therapies

Cell and genetherapies have been gaining a lot of attention in the medical and research communities. They offer customized medicine to individual patients, but the life-saving capabilities of these products come with an increased level of complexity. They must be manufactured safely, and individual batches must be tested to ensure they were created to specification.

Since the onset of COVID-19, many changes in the global supply chain have arisen as well, further complicating the manufacturing process and causing stalls in production to occur across many industries. Even the pharmaceutical industry, responsible for providing life-saving drug products to patients in need, has faced disruption. As a result, many companies are re-evaluating their manufacturing methods and switching to more efficient practices.

Contamination Events are a Lab’s Worst Enemy

Microbial contamination is a perpetual concern for these products. Cell and gene therapy manufacturing processes often include growth-supporting materials and media and individual microbes can quickly proliferate in these environments. Contamination ruins expensive products patients need, so testing in-process materials and final product is essential to stop it in its tracks. However, due to the presence of cells in these products,quality control microbiologists have run into challenges in testing for sterility, specifically with growth-based testing methods. In addition to the standard 14 days of incubation time, experts must now conduct lengthy sub-culturing steps in order to work around background interference.

Rapid Microbial Testing Reduces Time to Deliver to Patients.

How can rapid microbial testing technology be suited for the wide variety of materials that go into a cell and gene therapy? By working within the framework of the tried-and-true compendial methods that have been used for decades.

USP Chapters <61>and <71>, and their international counterparts, outline microbiological tests for non-sterile and sterile products. The chapters include membrane filtration methods to test large volume samples like water and small molecule raw materials.

The chapters also address direct inoculation methods for small volume and non-filterable samples, like cell-based preparations. All these methods require incubating media for an extended period to visually detect microbes.Products that appear cloudy in media, like cell-based samples, could require subcultures and extra incubation time.

Finally, A Rapid Solution for the Entire Manufacturing Process

The Celsis rapid microbial detection platform objectively analyzes that test media for the presence of microbial contamination using ATP bioluminescence. Depending on the product application, the 14-day sterility incubation can be reduced to 3-7 days. Results for in-process and non-sterile samples can be generated in 1-3 days. In all cases, these rapid results speed up contamination response and release to patients.

Most importantly, Celsis works. The platform can detect 1 CFU present in a product sample and can do so at a rate equivalent to the compendial 14-day incubation method. Celsis validation packages, designed to meet USP <1223>guidelines, even challenge this technology with known slow-growing microorganisms, like Cutibacterium acnes.

Insert image:

And with the new concentrator technology of the Celsis Adapt™, the Celsis method can detect ATP from microorganisms without generating false positives from product cell ATP. The procedure treats test media with a lysing solution that disrupts product cell membranes but does not interfere with microbial cell walls. The Celsis Adapt filtration process removes the product cellular debris while retaining microbes that may be present.

If microbes are detected, laboratories can use the original test media to subculture and identify the contamination for investigation. By getting an early result, the manufacturer can minimize the number of impacted batches. If all the hard work of the aseptic manufacturing design works out and the product result is sterile, great! Manufacturers can now release their product in less than half the time of traditional methods. With either result, manufacturers can take advantage of the Celsis rapid platform to ensure their cell and gene therapies reach patients quickly and safely.