Given the current pandemic situation, I thought it would be useful to review briefly the method FDA typically uses to approve flu vaccines (a virus with frequent variants) and which they might (and I believe likely will) apply to vaccines for variants of the Corona virus now in circulation. The approval of modified vaccines to virus variants is based less clinical information than is required for a completely novel vaccine (or novel new drug) because there is already a lot of information available from the clinical trials of the original vaccine.
The FDA criteria for approval of a novel flu vaccine requires a phase I/II and phase III studies. The object of phase I/II is to identify a dose regimen that generates an immune response high enough that it would be expected to prevent and/or mitigate the viral illness. The magnitude of immune response targeted is generally equal to or greater than the immune response associated with recovery from natural infection. A second objective is to determine the tolerability of the putatively effective dose regimen in a relatively small number of human subjects.
Once the dose regimen that accomplishes these two objectives is identified, FDA requires a Phase III study of a large number of subjects to show that the vaccine is still found to be well tolerated in a much larger number of subjects and that the vaccine really does prevent or mitigate infection sufficiently to support approval. Approval is based on a judgement that the side effects are more than compensated for by the reduction of infection or the consequences of infection.
Because flu virus variants change every year, it is not feasible to require this same development process every year, because the time delay required for a phase III study would mean the vaccine for the new variant would not be widely available during period when the variant(s) is prevalent.
To overcome this, once a successful Phase III study has been conducted for an specific vaccine, FDA requires only the phase I/II study of the vaccine for the variant, to confirm that the dose regimen induces an immune response to the variant similar to the immune response the original vaccine produced against the original virus. This shortens the development process for vaccines to variants substantially and is the reason that we have a new flu vaccine every year, just in time for the new flu season variant(s).
I think it is likely that FDA will follow this precedent for vaccines to the novel corona virus variants that may become predominant and for which the current vaccines may have lower efficacy. Once a vaccine has had a successful phase III study (and assuming nothing adverse has cropped up in the interim), approval of the same vaccine for a variant will not require a phase III study, just a successful phase I/II to confirm the immune response to the variant and tolerability in a small number of patients.
Given the incredible speed of current vaccine studies, I would guess that the vaccines for the new variants will be available within a couple of months. The current manufacturing procedures can likely be quickly modified to produce large amounts of variant vaccines. Thus, we likely could have EUA for variant vaccines soon if they are needed.
Here are some links to relevant FDA documents.
One other Covid item of interest is the upcoming FDA Advisory Committee Meeting that will review the J&J vaccine for an EUA. Here’s a link to the announcement that includes links to the webcast of the meeting.
The meeting materials and webcast will likely be the most complete summary of the clinical data on the J&J vaccine that is readily available for quite some time. Highly recommended for all those interested in the J&J vaccine.