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Authorities fear distrust of early preventives and complications for ongoing COVID-19 research.
As multiple COVID-19 vaccine candidates near the finish line for clinical testing, industry and government experts are contending with multiple issues related to testing and approval of effective preventives. At the recent meeting of FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC), leading scientists discussed policies and data requirements for determining that a pandemic vaccine is safe and effective when based on more limited, early trial data. A main goal for FDA officials was to reassure the public that it will take all precautions to ensure the safety of any vaccine approved under an Emergency Use Authorization (EUA).
The Center for Biologics Evaluation and Research (CBER) specified in its recent guidance that it expects an EUA application to provide two months or more of safety data for at least half of the participants in a trial following completion of the full vaccination regimen. As most serious side effects appear within six weeks of individual vaccination, this timeframe is designed to provide a sufficient period for detecting rare events such as vaccine-induced enhanced respiratory disease.
A particularly challenging issue for the advisors was how granting EUA status to an initial product would interfere with further assessment of the vaccine’s safety and with ongoing trials for other preventives. FDA and the expert panel want the sponsor of an authorized vaccine to continue blinded follow-up assessment to gain added safety information plus fuller comparisons among patient groups with differences in age, sex, comorbidities, and ethnic characteristics. And because data will be limited on how long immunity will last from initial vaccines, both manufacturers and regulators look to further assess when boosters might be needed.
While randomized, placebo-controlled clinical trials are key to understanding true effects of a medical product on larger populations, researchers and sponsors of initially approved vaccines fear it may be unethical to retain trial participants in a placebo arm following EUA approval. Some subsequent vaccines may affect certain populations differently, and varying formulations may be more suitable for distribution in certain regions. But continued development of alternative preventives may be hindered by difficulties in enrolling subjects in randomized trials when a vaccine is on the market.
FDA approval of the first vaccine will launch a complex and relatively untested process for delivering millions of doses to appropriate healthcare sites. Important complications are that some vaccines require two shots about three weeks apart and must be shipped frozen, one at sub-sub-zero temperatures. Additionally, it’s not clear how manufacturers, distributors, and public health officials will deal later with multiple approved vaccines with different potencies and administration schedules.
In hopes of avoiding the confusion and mistakes that stymied access to diagnostic tests and personal protective equipment when the pandemic erupted six months ago, the administration’s Operation Warp Speed has established a COVID-19 vaccine delivery system that involves a cadre of military logistics experts working with the Centers for Disease Control and Prevention (CDC), as outlined in a plan issued in mid-September. Initial vaccine distribution will follow recommendations of the CDC Advisory Committee on Immunization Practices (ACIP), which is expected to establish several phases for vaccine allocation. A CDC distribution contract with McKesson will handle the first vaccine deliveries from manufacturers to states and other jurisdictions, initially to treat front-line health workers and first responders.
Early vaccine distribution is expected to run through mid-2021, followed by phase two covering about 60 million to 80 million essential workers and high-risk individuals; the experts don’t expect a sufficient volume of doses for the general US population until mid-2022. Tracking a two-dose vaccination schedule promises to be confusing, as seen in the approach outlined by a CDC official at the FDA advisory committee: patients receiving a first dose will be given a card specifying time and type of dose to hand in at the second visit. “What could go wrong with that plan?” quipped one observer.
Jill Wechsler is Pharm Exec’s Washington Correspondent. She can be reached at firstname.lastname@example.org.