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Analytical Platform Methods: Caveat emptor!

The importance of passing the “Fit for Purpose” test!

During early development, we use a variety of laboratory analytical methods to characterize a promising biopharmaceutical molecule. Once we “know” our molecule, our role as analytical professionals shifts as we begin supporting process development to produce material for preclinical studies and beyond. The pressure to accelerate a molecule toward first-in-human trials often lead to selecting “established” analytical platform methods. Monoclonal antibody (MAb) development is a case in point. We know biosimilars may differ from the innovator molecule. Surely, with 55 full MAbs in Phase 3 development as identified by bioTRAK®, we know a priori that significant differences exist between MAb’s. For this reason, we need to ask ourselves if platform analytics truly pass the “fit for purpose” test for our molecule.

I have seen an increasing trend among Biotechs, especially those working with CDMO’s to adopt so-called platform analytical methods without applying the “fit for purpose” test. At some point, these so-called “platform methods” must be evaluated and demonstrated as “fit for purpose”.

Take for example a platform SEC method that uses a standard mobile phase. Will this method yield valid results when the SEC buffer significantly differs from the formulation buffer? What impact does the SEC buffer have on the MAb? Are the results reflective of the molecule? If you don’t know, you may be spending critical time and resources repeating method development activities at a later stage of development. Over the past several years, I have encountered more and more instances where companies merely accept the results of the platform method, without proper evaluation of “fit for purpose”.

It is acceptable to start with a platform method, but at some point, you must determine whether the analytical method is truly fit for purpose. For the SEC example above – are the results correct, i.e., does the method provide a suitable separation of high and low MW forms without effecting a change due to the mobile phase? An inappropriate method will yield inaccurate or even misleading information. As an analytical professional, you need to question the overall applicability of any platform method. Getting a number from a platform analytical method doesn’t necessarily mean it’s reflective of reality.

Given the criticality of the early development decisions, basing critical development program decisions on potentially flawed results due to the application of an inappropriate platform method can lead to problems at a later point during development, thus extending timelines and increasing costs. Consequently, “buyer beware” is the key when considering “platform analytical methods”.

Blog article by: Sheila Magil

The following two blogs written by my colleagues addressing other issues related to analytical methods specifically and broadly.


Scatter Correction for UV Absorbance Assays: A Cautionary Comment


Your Biologics CMO: Choose Wisely, Then Negotiate