A bioassay result is never certain. We are never able to measure the relative potency of a product, say, with 100% confidence that our answer is “correct”. There will always be an amount of variability in our measurements, due to both the assay condition and procedure. This is why results are typically presented with a…
The development of a bioassay is, in essence, a long series of choices. An assay which reaches commercial use is the end of a single path through a near-infinite forest of decision points and optimisations. The eventual goal is to produce an assay which is as accurate and precise as possible, while still being practical…
In the previous parts of our series covering the latest draft version of USP <1033>, we examined the goals of a bioassay validation study and the basics of accuracy and precision. Then, we discussed Probability of Out-of-Specification (Prob(OOS)) and how this can be used to inform the acceptance criteria for accuracy and precision in a…
In the first part of our series examining USP <1033> in depth, we discussed the goals of bioassay validation – specifically, to demonstrate that an assay is suitable for its intended use. Part of this demonstration is a detailed quantification of the accuracy and precision of the assay. We saw how accuracy and precision can…
During the early development of many therapeutic products, analytical and data management processes are often created quickly and pragmatically. Excel spreadsheets, macros, and bespoke code are widely used because they are flexible and allow rapid iteration while assays are evolving. And, since many novel products do not make it past the R&D stage, it rarely…
One can think of the life of a bioassay in two main acts. First comes the design and development of the assay, where the assay method is conceptualised, refined, and optimised. Later, the goal is for the assay to be deployed in a regulated environment to, for example, test batches of product to ensure that…
One common use for bioassays is to test manufactured biologic products before they are released to the wider consumer market. While all bioassays used for this purpose will have undergone stringent testing and validation, it is vital that their ongoing performance is closely monitored to ensure that any changes in the assay system do not…
It is far from a controversial statement that biologic therapeutics – such as monoclonal antibody and recombinant protein therapies – are complex and expensive to develop. As one might expect, therefore, the results of that development are also expensive when provided to patients, with per-patient annual costs for some commonly-used biologic therapies exceeding $20,000 in…
Statistics is hard, words are harder. So often when working through the statistics behind a bioassay, the correct path is obscured behind a word salad of jargon placed seemingly deliberately to block your passage. Our goal is to make statistics as accessible as possible, which is why we’ve previously examined the different limits one might…
So far in our series examining approaches to outlier management in bioassay, we’ve discussed the various perspectives on outliers held by stakeholders in the bioassay lifecycle and the problems the presence of outliers can pose for an assay system. We then used a simulation to evaluate the performance of a couple of methods for outlier…
Previously, we examined the reasons why one might consider attempting to identify and remove outliers from bioassay data. From a scientific perspective, omitting any collected data is never ideal, but true outliers are not part of the natural variability of the assay so ought not be included alongside legitimate observations. And, as we discovered through…
Outliers are among the topics which stimulate the most vigorous debate among the bioassay community. When a datapoint falls outside of the usual range observed for that metric, it sparks a series of difficult questions. Is that point an outlier, or is it a result of variability? How can we tell the difference? If it…
In many fields of science, researchers often face the challenge of measuring extremely small quantities. The life sciences are no exception, with experiments regularly requiring accurate and precise detections of tiny concentrations of impurities or other substances. Even while analytical techniques have advanced, manufacturing processes have improved in lockstep, meaning the capabilities of the testing…
In In Vitro vs In Vivo Potency Assays: Modern Vaccine Batch Release, we examined the pros and cons of two methods of testing vaccine potency: in vivo assays, which use animal models, and in vitro assays, which use laboratory experiments. As we established in that blog, the direction of travel is towards the improved analytical…
The previous blogs in our collaboration with the team at RoukenBio – the Immunology CRO redefined – have focused predominantly on the biological aspects of bioassay development. Including aspects such as cell selection and and DOE, we have been answering important questions about ensuring that the biological response in our assay is present, that it…
Bioassays are typically used to measure the properties of a manufactured product to ensure that it is of sufficient quality for use by patients. Inherent in this process is the need to make decisions based on the collected data. Is the potency of the product as expected? Are there any indications of the assay misbehaving?…
In the next part of our ongoing collaboration, the team at RoukenBio take a look at a key decision point early in the lifecycle of a potency assay: what cells to choose. Potency assays rely on cells as their foundation, acting as essential tools for measuring biological activity and ensuring therapeutic efficacy. The choice of…
A bioassay supporting a commercial product often has a lifespan of several years or even decades. Over that time, it is often necessary that the assay be performed in a number of different laboratories for a variety of reasons. And, in each, the same rigorous standards must be held to ensure that the safety and…
Therapies based on monoclonal antibodies (mAbs) are among the most powerful medical technologies to have been developed in recent years. From treatments designed to attack cancer cells and prevent rejection following organ transplants to methods for treating infectious diseases such as anthrax and COVID-19, the applications for mAbs continue to grow. And that’s before uses…
Management of the reference standard over the life of a product is critical to ensuring consistent production of material. We always want to be able to draw a link between a new batch being produced and one that has demonstrated acceptable clinical properties, particularly safety and efficacy. That’s why reference bridging is so vital: it…