FDA Issues Product-Specific Guidance Documents for Chloroquine Phosphate and Hydroxychloroquine Sulfate

April 15, 2020

On Tuesday, April 14th, FDA released two product-specific guidance documents for chloroquine phosphate tablets and hydroxychloroquine sulfate tablets, two drugs being investigated as potential treatments for COVID-19.  These guidances provide product-specific recommendations on, among other things, the design of bioequivalence (BE) studies to support abbreviated new drug applications (ANDAs).

The guidance, entitled Guidance on Hydroxychloroquine Sulfate was developed using the process described in that guidance and finalizes the draft guidance of the same title issued in April 2011. The guidance entitled Guidance on Chloroquine Phosphate is being implemented without prior public comment because FDA has determined that prior participation for this guidance is not feasible or appropriate in light of the coronavirus disease 2019 (COVID-19) public health emergency.

The guidance on Chloroquine Phosphate does not require an in-vivo demonstration of bioequivalence and only requires that the in-vitro dissolution profiles of the proposed products are comparable to those of the reference products.  The reference standard products are the chloroquine phosphate tablets manufactured by Natco Pharma Limited approved under ANDA 091621.

The guidance on Hydroxychloroquine Sulfate provides two options for demonstrating bioequivalence. Option one is to use the Biopharmaceutics Classification System (BCS)-based biowaiver; and option two is the more common in-vivo fed and fasting bioequivalence studies but measuring the hydroxychloroquine analyte in whole blood.  The reference standard product is Plaquenil® tablet manufactured by CONCORDIA PHARMACEUTICALS INC approved under NDA 009768.

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