Companies will continue to generate and maintain their own in-house standards for each specific monoclonal antibody therapeutic drugs, but the new NIST reference material provides a benchmark that all can share, especially useful for qualifying and validating methods for characterizing biopharmaceuticals up to the latter stages of product and process development.
Like other classes of drugs, mAb therapeutics go through an extensive clinical testing and regulatory approval process. However, mAbs are far more complex than small molecule drugs such as aspirin or statins, or simple biological drugs such as insulin. (See infographic.)
The entire production process spans weeks to months. And unlike small-molecule drugs synthesized in controlled chemical reactions that yield identical copies, mAbs are made by cells and may not be exactly alike, atom for atom. Yet, they must be so consistently similar that levels of safety and effectiveness are equivalent.
Throughout their lifecycle—from the start of production to injection into patients—mAb therapeutics undergo repeated rounds of testing and analysis, ultimately aiming to ensure that these products are of the appropriate identity, potency and purity, and that they can be reliably manufactured.
"The NISTmAb should help in answering a simple, yet critical, question that can consume a disproportionate amount of time when deviations arise with testing; is it the sample or the method that is varying?" said NIST's Michael Tarlov.
And for patients, said Kurt Brorson of the Food and Drug Administration (FDA), the "more robust and universally consistent" analytical methods fostered by NISTmAb should give a boost to their "confidence in the quality and consistency in the biopharmaceuticals and biosimilars that they need."
NIST RM 8671 should prove useful during regulatory evaluation of biosimilar mAb therapeutic drugs, follow-on versions of drugs at the end of their patent life. A biosimilar, according to the FDA, is a biological product shown to be "highly similar to an FDA-approved biological product, and has no clinically meaningful differences in terms of safety and effectiveness." Only minor differences in clinically inactive components are allowable in biosimilar products.
In early April 2016, the FDA approved the first and only biosimilar mAb therapeutic in the United States, a follow-on version of infliximab, which is approved for treatment of rheumatoid arthritis, Crohn's disease and several other disorders. With patents expiring on six other mAb-based therapeutics by 2020, a batch of biosimilar applications for FDA approval is anticipated.
For both regulators and biosimilar developers, NIST's John Schiel explained, the NISTmAb can serve as an "anchor molecule." It can be used, he said, to evaluate whether analytical methods are useful for reliably determining whether a follow-on compound, likely made with substantially different manufacturing technology, is sufficiently similar to the originator molecule. If, for example, comparisons of molecular structure differ, measurements on the NISTmAb could be used to establish whether the difference is real—caused by, say, a true structural divergence—or due to an artifact, or peculiarity, of the instrument or method used.