COVID-19, the disease caused by the SARS-CoV-19 virus, is complex, and the number, type, and severity of symptoms often vary from patient-to-patient. COVID-19 complications and outcomes can vary by age, the presence of co-morbidities, and gender. At the same time, the virus has been documented to target multiple organs, including the lungs, heart, kidney, nervous system, liver, and intestines. Treatment for each patient, therefore, must be individualized—taking into account both the severity of symptoms, and the organs that are being afflicted.
At present, there are no drugs that are U.S. Food and Drug Administration (FDA) approved to treat COVID-19. A number of drugs, and vitamins, are being evaluated clinically for statistically significant evidence of efficacy against COVID-19. Drugs which effectively treat COVID-19, COVID-19 vaccines, and the ability to accurately test individuals for COVID-19 on a national scale, are thought to be crucial to saving lives and "re-opening" the economy.
Two of the drugs being evaluated as potential treatments for COVID-19, chloroquine phosphate and hydroxychloroquine sulfate, have received significant attention. These two drugs, originally approved as anti-malarials, are also used to control auto-immune diseases, including lupus and rheumatoid arthritis.
Under an emergency use authorization, the drugs can be used to "treat COVID-19 in adults and adolescents who weigh at least 50 kg, and are not able to participate in a clinical trial." And while several drug manufacturers, including Mylan and Sun Pharmaceuticals, have committed to donate hundreds of millions of doses of these drugs, the FDA is concerned that enough dosages be available to meet growing demand. The FDA therefore recently issued two short guidances (here and here) to aid developers of these drugs.
The hydroxychloroquine sulfate guidance supplements an earlier guidance, and discusses, among other things, that the agency will consider a BCS-Class 3-based biowaiver so long as waiver applicants provide "appropriate documentation regarding high solubility, very rapid dissolution, and that test product formulation is qualitatively the same and quantitatively very similar …" In the absence of seeking a biowaiver, the guidance provides the option to conduct fed or fasted state in vivo bioequivalence studies, and notes any study should measure "hydroxychloroquine in whole blood" as the analyte.
The chloroquine phosphate guidance clarifies that the product is AA rated in the Orange Book, meaning that there are no known or suspected bioequivalence problems, that biowaivers are available, and provides specific dissolution test information (and a link) to be used to support a biowaiver petition, including that biowaiver testing should include "comparative dissolution testing on 12 dosage units for both strengths of the test and reference products."
