When we calculate a relative potency, we find the shift between the dose-response data from two samples. This is usually done by performing a calculation using the parameters from statistical models fit to the dose-response datasets. Clearly, therefore, we must estimate the model which best fits the data. This is a process which is –…
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…
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…
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…
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…
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?…
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…
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…
So, you’re confident that you’ve got a feasible assay with a well-defined dose-response curve. But bioassays, as we all know, are fickle. The observed responses are sensitive to many factors which can lead to appreciable variability in the experiment and, in turn, a high assay failure rate. An important part of the development phase of…
Vaccines are among the most important technological developments in human history. From the earliest attempts to prevent smallpox by variolation to modern mRNA vaccines built without a virus needing to have entered the development lab, the vaccine has become a vital string in the bow of public health officials. As with all medicines, batches of…
One of the most frequent topics of discussion on this blog has been the correct and optimal utilisation of different classes of statistical models with bioassay data. Most common among these are the four- and five-parameter (4 and 5PL) models, alongside the simple linear model. There is, however, stranger at the feast: the three-parameter logistic,…
Bioassays serve as a method of testing a product: does the latest batch of our biologic have an acceptable potency? To do this effectively, we need to ensure that our test system – the assay – continues to function as it was originally designed. This is crucial as, in the worst case, a flawed assay…
In bioassay analyses, there are three statistical models that are commonly fit to dose-response data: the linear model, the 4PL model, and the 5PL model. We’ve examined the properties of the 4PL model in great detail previously, and the time has come to give the 5PL model a similar treatment. The 5PL model is the…
At the forefront of medical development lies the world of cell and gene therapy. Unlike traditional, small molecule therapeutics, treatments based on biologics can treat, cure, or even prevent genetic conditions such as sickle cell anaemia and muscular dystrophy. They can also be tailored to individual patients, giving the potential for personalised treatments for certain…
A concept we’ve discussed several times over the years is that of homogeneity of variance. We highlight it so regularly as it’s among the most critical properties that relative potency data must have before valid statistical inference can take place, and often requires careful consideration to realise. We’ve previously covered one common way to ensure…