Therapeutics Development: Keeping Critical Quality Attribute (CQA) Analysis Simple and Data-rich
Critical quality attributes (CQAs) are essential benchmarks for quality during process development of therapeutics in many disease areas. We spoke with Dr. Kishore Katikireddy, External Collaborations Project Manager at Sartorius, about the importance of CQAs, the challenge of selecting the right ones and how the right equipment can simplify the process.
This article is posted on our Science Snippets Blog
What are critical quality attributes?
According to the ICH Guideline for Pharmaceutical Development, critical quality attributes (CQAs) are physical, chemical, biological or microbiological properties or characteristics that should be within an appropriate limit, range or distribution to ensure desired product quality.
CQAs collectively act as the gatekeeper for making a successful cell therapy, immunotherapy, or other drug. CQAs are not only required for upstream steps but are also an essential part of quality control throughout your processes. This includes downstream steps like manufacturing, which are scrutinized by regulatory bodies.
Finding the right CQAs
Selecting which attributes to measure can be a challenge. The right attributes must have solid footing in experimental evidence to show they are linked to the efficacy and safety of the final product. Timing also matters; CQAs need to be measured at critical time-points during the process.
Dr. Katikireddy explains this using an example for workflows involving induced pluripotent stem cells (iPSCs). “When you’re differentiating iPSCs into cardiomyocytes or pancreatic cells, you need to make sure that you have the right cells after adding growth factors. So, you must test in the middle of the process to see if you’re getting the expected cells.”
Quantifying live-cell health and function
Once you select the right CQAs, you need to establish assays and equipment that measure selected markers quickly and reliably. Cell health and functional assays are straightforward on high-throughput systems that have validated cell assays for proliferation, apoptosis, tumor cell killing, antibody internalization and more - such as Incucyte® Live-Cell Analysis Systems
“The Incucyte system lets you see tumor killing as it happens and measure the kinetics,” explains Katikireddy. “Let’s say you’re working with engineered CAR-T cells that target pancreatic solid tumors. With live-cell imaging you can watch the immune cells kill the cancer cells and quantitate this process in the CQAs before moving on to clinical applications.”
Adapting to advanced cell culture systems
Ten years ago, we were only focusing on 2D adherent cell cultures. Now there is a shift toward more physiologically relevant 3D cultures that better mimic the complex tumor environment. Innovations in culturing and analyzing complex cell culture models are enabling new clinical applications using these models.
“We partner with scientists to help them simplify their process and drive richer data from complex cell culture models, like organoids and spheroids,” adds Katikireddy. "The data is accurate and reproducible, thus reducing the need for as many repeated experiments. That in turn helps reduce the cost of the final therapeutic for patients. That is the goal.”
Read more about the Incucyte® Live-Cell Analysis System and Live-Cell Assays to learn why so many scientists are finding them indispensable for simple and reliable validation of cell phenotype and morphology.
