At BioPharmaSpec we are increasingly being asked about Analytical Quality by Design, or AQbD (1), and whether we implement this concept in our studies and methods. The simple answer we give is that we always have! Analytical Quality by Design is a concept that we should all be following when developing methods for analyzing biopharmaceuticals.
|Systematic approach to method development, optimization and analysis|
|The objective is to understand the method in depth to avoid unexpected and OOS results or issues with the method down the line|
|Most of the work is performed in the Method Development stage where all the critical operator and method parameters need to be assessed|
|This approach should generate a robust method for analytical assessment going forward|
|The risk of needing significant change to the method and re-qualification or re- validation is then minimized|
AQbD is a systematic approach to developing and optimizing methods in order to ensure analytical methods are reliable and robust. Most, if not all, of the effort in this regard should be included in the development phase, with testing being performed to establish any weak points in the method. If any are found, then the method should be improved or sufficiently controlled such that the risk of re-development, further method optimization and re-qualification/re-validation is minimized. The more effort that is put in to testing the reliability of the method during development, the more you will know about your method and the more robust the end method will be.
It is also important and helpful to have a strong knowledge base regarding the methodology being developed. The importance of a knowledge base covering the characteristics of the applicable methods for testing any given product, including what limitations they may have and what orthogonal methods can be used to give fuller or supportive data, was covered in a previous blog.
There is an additional concept within BioPharmaSpec’s method design concept which relates to an understanding of the expected experimental error for the method being developed. Many of BioPharmaSpec’s current analytical programs are focused on the question of whether a new batch of a product is comparable to the previous or whether a biosimilar is comparable to an innovator reference product. To be able to conclude whether two or more products are comparable requires a knowledge of the expected experimental variance for each of the methods employed.
This is why every method that BioPharmaSpec provides is developed according to the concepts in the table above, as has always been the case. Methods can then be qualified according to ICH Q2(R1), with an eye on the new revision ICH Q2(R2), using standard peptides, proteins, glycoproteins or oligosaccharides as appropriate. Critical methods (i.e. those being used to make critical decisions about the product and those that are destined to potentially become release tests) are also qualified using the product itself with the reliability, robustness, specificity, repeatability, intermediate precision, linearity and accuracy of the method being assessed as appropriate for the methods use.
In summary, although AQbD is being discussed as a new concept that the analytical scientist should be strongly considering, in our eyes it is something that we have simply always done in order to provide the most reliable and robust methods for assessing structural and physicochemical properties of biological products.