Recently, we’ve noticed a number of commentary articles appearing discussing the problems of validation and reproducibility of antibodies:
The authors and interviewees have primarily been associated with academic institutions or antibody suppliers. However, this is not a new a new issue and pharmaceutical scientists have been aware of it and taking action on it for a number of years.
In 2012, the Ligand Binding Assay Focus Group of the Biotechnology section of the American Association of Pharmaceutical Scientists published a white paper as part of their “Ligand Binding Assays in the 21st Century Laboratory” series of publications. The paper is “Recommendations for Characterization and Supply of Critical Reagents.” In this publication the authors summarize the key considerations for the generation, production, characterization, qualification, documentation, and management of critical reagents in ligand binding assays (LBAs). Ligand binding assays include any type of assay using affinity reagents.
LBAs are used during every phase of the drug development process from discovery to post-market monitoring. Pharmaceutical scientists jobs, and the products’ efficacy and safety, depend upon LBA reagent quality and consistency. Therefore, great importance is placed on the structural integrity, stability, and performance of LBA reagents.
Many of the critical reagents you might use in LBAs, such as monoclonal antibodies, polyclonal antibodies, fusion proteins, enzymes, or detection molecules, are produced via biological processes and are thus inherently prone to variability among different production lots.
Since the lifespan of a drug, from development to the end of its production, can span more than 20 years, establishing criteria and a stable supply for critical reagents, such as antibodies, is critical. This is something that most academic labs don’t have to concern themselves with, as their project timelines are much shorter and the impact on users is less severe than the safety and efficacy of a drug.
LBAs may be used anywhere from six weeks to six months in the preclinical stage, six months to five years during the clinical development stage, and possibly more than 20 years to support post-marketing activities and manufacturing. Even in the preclinical stage it’s critical that reagents be trustworthy, as the assays may get passed on from teams in the preclinical groups to teams in clinical research. Nobody wants to pass along a bad assay.
In September 2015, ThermoFisher announced it is sponsoring an International Working Group on Antibody Validation. This will be an independent group with some funding supplied by ThermoFisher. The interesting thing we noticed is that not one member of the working group is from pharma or biotech, instead they are all from universities or academic research centers. Pharmaceutical scientists seem to have grappled with this issue already and come up with some solutions. Unfortunately, it’s harder for pharmaceutical scientists to share their information as readily as those in universities and government research institutions. Perhaps these new teams working on the issue of antibody validation should engage with some pharmaceutical scientists and diagnostic company scientists, as both of these types of entities have had to solve these antibody issues already.
What are your thoughts on antibodies as critical reagents and how to validate them?