On the Federal Register prepublication page (here), the FDA gives notice of the finalization of two guidance documents providing bioequivalence recommendations for two drug products that have received a lot of recent news attention, chloroquine phosphate and hydroxychloroquine sulfate. The two products have received attention because of the COVID-19 pandemic and the anecdotal reports of the potential for them to have some activity against the viral infection.
The chloroquine phosphate recommendation (here) is being issued and finalized without public comment under the public health emergency and calls for a waiver of in vivo bioequivalence study requirements if the product meets appropriate dissolution specifications. This waiver is available because chloroquine phosphate is a DESI effective drug (however not for COVID-19) with no known or suspected bioequivalence problems.
Hydroxychloroquine sulfate recommendations (here) were initially made in April 2011 and are being finalized today. There are two options to establish bioequivalence for hydroxychloroquine sulfate. First, the Agency notes the product may be eligible for a waiver of in vivo bioequivalence study requirements under the FDA’s BCS guidance as a Class 3 product; that is, a highly soluble, rapidly dissolving product with low permeability. The FDA says a decision on the acceptability of the waiver will be based on the data submitted in the application. Secondly, a firm may choose to perform fasting and fed, single-dose, two‑treatment, randomized, parallel in vivo studies, along with appropriate comparative in vitro dissolution studies.
The FDA had been under increasing pressure to issue an emergency use authorization (and it did on March 29, 2020) for these two products in the wake of the coronavirus pandemic, even though there is scant available data that support the products’ effectiveness against COVID-19 in humans. Much of the pressure has come from the White House as the President continues to tout these drugs, despite the lack of scientific support for their use. There are currently ongoing studies to determine whether the products demonstrate effectiveness and at what doses they do so. While the safety of these two drugs has been established based on prior FDA approvals for other indications (including malaria, rheumatoid arthritis, and systemic lupus erythematosus), the drugs do have significant and potentially serious adverse events associated with their use.