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FDA issues potency testing guidance for COVID antibody treatments

Posted 14 January 2021 | By Kari Oakes 

FDA issues potency testing guidance for COVID antibody treatments

Amid the coronavirus pandemic, the US Food and Drug Administration has issued guidance on potency assays for manufacturers of monoclonal antibodies and other therapeutic proteins to treat COVID-19. The guidance is immediately effective for the duration of the public health emergency.
In the ordinary course of business, FDA would have engagement with drug developers to work on potency assays “over a span of years.” However, according to the guidance, “given the compressed development timelines associated with therapeutics intended to treat COVID-19, FDA is issuing this guidance to provide more detailed recommendations to drug developers with the goal of facilitating more complete submissions.”
The agency intends to support “all scientifically sound approaches to attenuating the clinical effect of COVID-19,” and to do so expediently as the pandemic continues largely unabated. In general, potency assay methods should provide comprehensive assessment of the known or potential mechanisms of action of the monoclonal antibody or protein and should also be sensitive enough to demonstrate lot-to-lot consistency.
Therapeutic agents falling under this guidance may come to the FDA through the emergency use authorization route, but sponsors may also submit investigational new drug applications or biologics license applications. The guidance details the various mechanisms by which monoclonal antibodies and therapeutic proteins such as scaffold fusion proteins might ameliorate the effects of COVID-19.
In terms of specific methods, binding assays will generally be sufficient to support a submission and generally will be developed during the early stages of product development.  “Although helpful in the initial phases of development, these assays do not directly confirm the product’s ability to inhibit the target protein’s activity and should not be used in lieu of methods that confirm potency,” cautioned FDA in the guidance.
When a product is meant to keep the SARS-CoV-2 spike protein from binding to ACE2 – the point of the virus’ entry into human cells – FDA recommends a potency assay since it is a “better reflection of the intended mechanism of action.”
Viral neutralization assays, said FDA, are a more comprehensive way to assess both mechanism of action and potency. In vitro neutralization assays should be established early in the development process.
The guidance walks developers through the steps of SARS-CoV-2 virus entry into cells and addresses key considerations for several types of viral neutralization assays. Fc-effector function assays are also addressed; “FDA recommends including an FcγRIIIa-mediated/natural killer cell antibody-dependent cell-mediated cytotoxicity assay, as that appears to be the most sensitive to changes in glycosylation.”

The guidance also lays out additional considerations to be addressed when sponsors develop their potency assays for these products, including the importance of using isolates prevalent in the HS, providing genome sequences or GenBank IDs, maintaining a master cell bank, and other considerations.
FDA also acknowledges that “novel mechanisms of action that are not addressed in this guidance may be identified in the future,” so sponsors should consult individually with the agency in these cases.
Convalescent plasma is explicitly excluded from the guidance, as are hyperimmune globulins, vaccines, and cell and gene therapies.



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