As the outbreak of a novel coronavirus accelerates in China, and sporadic cases appear elsewhere in Asia, North America, Australia, and Europe, there is intense interest in the development of a vaccine, and several U.S. drugmakers have begun working on them with the National Institutes of Health
As the Wall Street Journal noted in a Jan. 30 editorial, "It took scientists 20 months to develop a SARS vaccine to test on humans, but the NIH hopes to have a vaccine ready for human trials by April."
If they can meet that timeline, good for NIH, but then its sibling agency, the Food and Drug Administration, gets into the act. And that's a problem.
The FDA had a significant role in a debacle surrounding a vaccine against swine flu virus almost a half century ago, and regulators have a long memory. Of the 45 million people vaccinated against the swine flu in 1976, 450 developed a serious adverse reaction — the rare, paralytic Guillain-Barré syndrome. What made the situation even more unfortunate is that the predicted epidemic never materialized, so the vaccine wasn't needed.
Since then, the regulatory bar has been very high for approval of vaccines that would be administered to vast numbers of healthy people. For example, before approval, the first rotavirus vaccine (RotaTeq) was tested on 72,000 healthy infants, and the first human papilloma virus vaccine (Gardasil) on more than 24,000 people.
Just planning and getting clinical trials of that magnitude under way would be a major undertaking – recruiting medical practitioners and research institutions and obtaining permission from local Institutional Review Boards, to say nothing of actually producing sufficient vaccine (under stringent Good Manufacturing Practices conditions) for the trials. Then comes the accumulation, organization, and analysis of the data, first by the sponsors of the vaccine, then by regulators.
Without belaboring the point, the FDA's record on vaccines is less than sterling. The agency was woefully slow, lagging behind other countries, in approving the first vaccine against meningococcus B, a life-threatening bacterial infection. Regulators have also erected post-approval obstacles. A decade ago, the FDA asked pediatricians to "pause" in administering Rotarix, a vaccine made by GlaxoSmithKline that prevents rotavirus infection, a diarrheal illness that can cause severe dehydration. The rationale was that small amounts of DNA from a pig virus had been detected in the vaccine preparation. That might sound like a good reason for concern — except that the FDA itself confirmed that the material was present throughout the vaccine's development.
In other words, all of the studies that confirmed the safety and efficacy of the vaccine had been performed with the viral DNA present, and according to the FDA, "extensive studies, including placebo-controlled, randomized clinical studies involving tens of thousands of vaccine recipients, support the safety and effectiveness of the vaccine."
More specifically, no safety problems emerged from the pre-approval clinical trials in 90,000 subjects or during postmarketing surveillance covering more than 69 million doses of the vaccine. The head of the agency, Margaret Hamburg, even announced, "We're not taking this action on the basis of a safety concern." So what was the basis – her horoscope? She never explained it.
Consider these facts as well: The virus is commonly consumed in pork products and does not cause disease in any known host, including humans and pigs. One must wonder, then, what the problem was that the FDA was trying to fix by interrupting the use of the vaccine.
The story gets better: Regulators requested the Rotarix pause, in part, because of the availability of an alternative vaccine, RotaTeq, produced by Merck. But using a new, high-sensitivity assay, Merck soon thereafter detected DNA fragments from two pig viruses in its vaccine. So, did FDA officials also pause the Merck? No — instead, they rescinded the recommended pause on administration of Rotarix, the GlaxoSmithKline drug.
The drugs were, and are, clearly safe on the basis of the extensive clinical trials and post-approval surveillance, but the FDA appeared to be making its decisions in order to protect itself, rather than to protect public health. Regulators' bumbling fueled the hysteria of anti-vaccine activists, and some parents were sufficiently confused that they delayed vaccinating their children, endangering them. Thus, regulators created a wholly gratuitous public health problem.
And by the way, the SARS vaccine mentioned in the first paragraph was never commercialized. The outbreak faded away.
A coronavirus vaccine in the foreseeable future? I'm not holding my breath.
Miller, a physician and molecular biologist, is a senior fellow at the Pacific Research Institute. A 15-year veteran of the FDA, he was the founding director of the agency's Office of Biotechnology.