With record speed, little more than a year after Covid-19 first hit the headlines, the global drug industry has developed a growing number of vaccines that prevent severe disease and slow the spread of the virus. Yet the deployment of these vaccines has fallen short of hopes and expectations. Time is of the essence, with new virus variants looming and the summer offering a preciously short window to push the virus out of circulation before its reproduction rate rises again in the fall.
The main holdup in the distribution of the vaccine relates to manufacture and supply. The two mRNA vaccines currently authorized in the United States, from Pfizer and Moderna, are highly complex to manufacture and require two doses; only 53 million doses have been sent out for distribution so far. A third vaccine, from AstraZeneca, has been administered to millions in Britain but is not likely to be available in the United States for several more months because the Food and Drug Administration has yet to approve it. Congress should investigate whether this delay is justified.
The constraint on production has caused states to ration distribution and prevented medical providers from simply administering vaccines to whomever turns up. Indeed, most retail clinics and physician offices that typically administer the flu vaccine are not administering any Covid shots. Furthermore, many state-run facilities specifically established to administer the vaccine to priority groups have been closed for lack of vaccine supply.
“The entirety of our week seven allocation was delivered to providers yesterday and already New York has administered 90 percent of its first doses while prioritizing fairness and equity,” New York governor Andrew Cuomo lamented. “Week after week we exhaust our vaccine supply and are basically left waiting for the next week’s delivery.” Cuomo noted further that “This is not unique to New York, it’s happening in states across the nation.”
The Pfizer and Moderna vaccines account for less than half the volume of vaccines for which the federal government had initially secured purchase agreements. AstraZeneca’s vaccine (of which the United States has purchased 300 million doses) is awaiting FDA approval. The company’s Baltimore factory is already manufacturing millions of doses, but these are not expected to be approved for distribution until April.
The precise clinical benefit and risks associated with pharmaceutical products—unlike most consumer products—cannot easily be ascertained by the untrained eye or by public reputation. Most of the expense associated with drug development results from demonstrating safety and efficacy in costly placebo-controlled clinical trials. (While the Moderna vaccine was designed in only two days, it took most of the year to test in three standard phases of assessment. Other rival drugs, also designed rapidly, stumbled in trials.) The FDA therefore plays an essential role in certifying the value of pharmaceuticals, keeping them off the market unless they pass exacting trial thresholds. Drugmakers and patients, in turn, benefit from this arrangement, which distinguishes genuinely effective therapies from crank therapies.
Given typical side effects with potent pharmaceutical products, the regulatory task of balancing safety and efficacy is often challenging—and particularly so in the case of vaccines, since any approved product will be administered to tens of millions of healthy individuals. Even rare casualties might adversely affect public willingness to seek vaccination. Once approval is granted, products become harder to withhold, and the FDA loses much of its leverage to insist that safety concerns be addressed.
AstraZeneca reported initial results from its clinical trials in December but acknowledged errors in the dosage administered to a significant number of study participants. The full trial reported efficacy lagging that of the Pfizer and Moderna vaccines for those receiving the intended dose; AstraZeneca then claimed inflated efficacy based on a small subset of trial participants that had inadvertently received an alternative dosing regimen. The FDA is waiting for the results of U.S.-based clinical trials to clear up the confusion.
By contrast, the British government (which sponsored the development of the AstraZeneca vaccine) approved it on December 30—with a pledge of 2 million doses per week by mid-February. The daily rate of vaccination in Britain, which had previously grown at a similar rate to that in the United States, is now rising significantly faster. On January 29, the European Union (which has trailed far behind both the U.K. and the U.S. in vaccine deployment) followed suit and approved AstraZeneca’s vaccine.
Beyond the question of efficacy in directly protecting vaccine recipients from severe illness, researchers have now demonstrated significantly reduced transmissibility associated with the AstraZeneca vaccine. Given that millions of Britons have now received the vaccine without widespread adverse consequences, some experts have begun to recommend that the U.S. should follow the EU and U.K. by immediately approving the vaccine, without waiting for additional clinical trial results.
It would be a huge scandal, of course, if the AstraZeneca vaccine were approved and led to the deaths of thousands of recipients. But why is the delay in the vaccine’s approval—as it is being successfully used elsewhere—not causing an outcry of its own?
The FDA’s strength is that it adheres rigidly to scientific rules. This affords it freedom from politics and the ability to stand up to powerful drugmakers—and it allows the agency to insist that manufacturers incur billions of dollars in costs needed to prove safety and efficacy.
Yet even the best bureaucratic rules are artificial constructs, generalizations constructed for ordinary cases that may prove inadequate in extreme or extraordinary circumstances. Doubts about the AstraZeneca vaccine’s efficacy involve only whether the efficacy is moderately high or very high; the accumulated evidence from vaccination of millions in Britain suggests that safety issues may be minimal. The primary concern regarding swift approval is therefore that it would undermine the FDA’s reputation, encouraging drugmakers to flout rules or cut corners in future development.
These worries are understandable, but less laudable concerns exist, too—like the tendency of bureaucrats to hide behind rules. No one is worried about getting fired for approving a safe vaccine too slowly, but the FDA may fear a loss of power if it bends too easily in granting approval. At the same time, advance-purchase guarantees from Washington mean that AstraZeneca will get paid regardless of whether its vaccine is approved early or late—and so the company may lack the usual incentive to push things along.
Those who favor withholding the AstraZeneca vaccine for another two months argue that pushing for immediate approval would represent siding with politics over science. Yet, the calculus of risk embedded in existing FDA procedures was itself the product of politics—albeit the politics that had different challenges in mind.
Political intervention to waive FDA rules to approve the AstraZeneca vaccine immediately would come at a cost to the FDA’s reputation—and that should not be ignored. But Congress should not assume that inaction is cost-free, either. Given the circumstances, elected officials should not hesitate to ask questions and hold the FDA’s feet to the fire. The Biden administration should insist that the risks of doing nothing be weighed against those of early approval, while Congress should hold hearings to make the trade-offs more clearly understood.
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