Given the increased demand for chloroquine phosphate and hydroxychloroquine sulfate, which are being used off-label and in clinical trials in the U.S. and many other countries to treat COVID-19, the FDA issued final product-specific guidances to support generic drug development for the antimalarial drugs. The guidance for hydroxychloroquine finalizes a draft issued nine years ago and adds advice about a Biopharmaceutics Classification System-based biowaiver option. The guidance for chloroquine is the first the agency has issued for the drug and is being implemented without prior public comment because the “FDA has determined that prior public participation for this guidance is not feasible or appropriate,” according to a notice slated for publication in the April 14, 2020, Federal Register. The guidance clarifies that chloroquine phosphate has an AA rating in the Orange Book, which means it has no known or suspected bioequivalence problems and no in vivo studies are necessary. Both guidances are being implemented immediately.
The first patients have enrolled in the NIH’s ORCHID trial that’s testing hydroxychloroquine as an add-on to standard of care in treating COVID-19. The blinded, placebo-controlled, randomized trial is intended to enroll more than 500 adults who are hospitalized with the coronavirus or in an emergency department with anticipated hospitalization. Preliminary reports from small studies have suggested the drug may have potential efficacy against the virus, according to the NIH. That’s led to demand for the drug without a lot of safety and efficacy data to support its use in COVID-19. “Many U.S. hospitals are currently using hydroxychloroquine as first-line therapy for hospitalized patients with COVID-19 despite extremely limited clinical data supporting its effectiveness,” said Wesley Self, an emergency medicine physician at Vanderbilt University Medical Center and the PETAL Clinical Trials Network investigator leading the trial. “Thus, data on hydroxychloroquine for the treatment of COVID-19 are urgently needed to inform clinical practice.”
Success in a petri dish does not mean a drug will be safe and effective against COVID-19 in humans, the FDA is warning, as it cautions people not to take ivermectin approved for animals. The agency is concerned that a recent research article describing the effect of ivermectin, an antiparasitic, against the coronavirus in an early lab test could lead to people self-medicating by taking ivermectin products intended for animals. The concern comes after a man died when he ingested fish food that contained chloroquine phosphate. “People should not take any form of ivermectin unless it has been prescribed to them by a licensed health care provider and is obtained through a legitimate source,” the agency said. Ivermectin is approved in tablet form for use in people for the treatment of some parasitic worms and in topical formulations to treat external parasites such as headlice and skin conditions such as rosacea. Veterinarian formulations are approved for prevention of heartworm disease in some small animal species and for treatment of certain internal and external parasites in various animal species.
The European Commission, EMA and the European medicines regulatory network have developed a question-and-answer (Q&A) guidance on regulatory expectations for human drugs and flexibility during the COVID-19 pandemic. With a focus on crucial medicines used to treat patients infected with the virus, the guidance discusses marketing authorizations and regulatory procedures, quality variations, manufacturing and importation of active pharmaceutical ingredients and finished products, and labeling and packaging requirements with flexibility to facilitate the movement of drugs within the EU. The guidance will be continuously updated.
Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) updated its Q&A guidance on how to manage clinical trials during the COVID-19 pandemic. The guidance provides information on alternative measures that can be used when a process predetermined in the study protocol is not deemed feasible due to COVID-19, such as when participants can’t visit the site to receive study drugs, devices or other products used in the trial. “In any situation, protection for the safety of trial participants should be given first priority, and any changes/deviations from the study protocol should be well documented,” the PMDA said. The agency also is allowing institutional review boards (IRB) to meet via email or virtually when an immediate meeting is necessary to enable a quick start of clinical trials for COVID-19 products. The actual process and conduct of such meetings should be well noted, the agency said.
The FDA is extending the deadline until June 5, 2020, to apply for a funding opportunity to examine the use of real-world data (RWD) to generate real-world evidence (RWE) in regulatory decision-making. The agency said it is particularly interested in projects that compare the use of RWD and generation of RWE with more traditional approaches and methods for data collection and evidence generation. The scope of the funding opportunity includes projects that focus on exploring and conducting innovative clinical trials, explaining ways to address challenges to using RWD in research studies, exploring the use of innovative technologies, designing and conducting pilot projects, determining endpoints that RWD can capture, and evaluating reliability considerations around the use of RWD.