The truth is; the accuracy and robustness of any process under development or manufacturing outcome is only as good as the reliability of the assays needed to understand the process. The effort involved to get to a comfortable situation where all necessary tests are available, is often highly underestimated. For instance, let me tell you what’s involved in developing a standard and widely used assay, like an ELISA-based assay to measure host cell protein (HCP).
Testing for host cell protein
An analytical assay to test the concentration of HCP in a sample is required for all classes of biopharmaceuticals, such as vaccines, viral vectors or recombinant proteins. Residual proteins derived from the production cells could reduce the efficacy of the product. But more importantly, they could have potential toxic or immunological consequences for the end-user. Because companies widely use this assay, they typically performed this assay many times. So, why is it still necessary to do development on this assay? To answer that question, you have to realize that every deviation in a manufacturing process influences the outcome of what an analytical assay may detect. Therefore, working with another cell line or another matrix requires the team working on analytical assays to demonstrate that the assay in question is still robust, reliable and fit-for purpose.
Developing an analytical assay for R&D and GMP purposes
Before starting the development of an assay, it is important to realize what type of material you will be measuring; soluble or membrane-bound; in what matrix; the stability determining parameters (storage time and conditions); is a quantitative or qualitative output parameter required; and finally, what is the expected throughput of sample analyses (manually or automated format)?
In addition, for the most optimal production process, you generally want to be able to measure within a wide range to accurately assess how process parameters influence the end result(s). For instance, in the case of the HCP assay, the use of a different filter, when developing or optimizing a purification process, may have significant impact on the amount of HCP in the sample. The assay must therefore be fit to accurately measure relatively high concentrations of HCP. This is needed before optimization of the purification process. The assay must also be able to measure low concentrations for when a process is fully optimized. At this stage, the different assay parameters, e.g. accuracy, specificity, precision, linearity, need to be determined for each specific matrix. The outcome of the analytical assay development needs to provide a reliable starting point for the next stage; validation of the assay.
The validation of an assay requires comprehensive experiments. These experiments evaluate and document the quantitative performance of an assay. Validation uses the input of assay parameters determined during the development phase. It is essential to understand which of the results are needed for in-process control and which are pivotal for release of the product. The tests required for product release must adhere to ICH Q2 guidelines. The company’s Quality Control (QC) team usually performs these tests.
Analytical assay development at Batavia Biosciences
In most organizations the analytical assay team is separated from the QC team. Hence, assay development and assay validation require a (internal) tech transfer. In contrast, at Batavia Biosciences, the Analytical Assay Department is integrated in the QC department, and therefore the team is able to develop, validate and execute analytical tests for R&D and GMP. This team of experts is at the heart of the company’s process development. As such, they are well positioned to support smooth transition for any biopharmaceutical from the laboratory bench to the clinic.
We are dedicated to help bring biopharmaceuticals to the market at higher speed, with reduced costs, and with a higher success rate. Batavia Biosciences has vast experience in developing and validating assays. Our team of experienced assay specialists is well equipped to take on any challenge associated with biopharmaceutical testing.