In this episode, approval of an Ad5 vectored SARS-CoV-2 vaccine for the military in China, description and clinical trials of a Novavax vaccine joining Operation Warp Speed, prevalence of SARS-CoV-2 in Spain, shedding and transmissibility of the virus, and listener email.
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Mike Olive says
First of all, let me say how much I enjoy your podcasts. During this pandemic, my exercise routine consists of walking about seven mile a day (wearing a mask), which takes me exactly the length on one of your shows. So in addition to being full of fascinating science, it keeps me healthy. I am a retired microbiologist/virologist, but I currently work as an independent consultant for companies designing new diagnostic technologies for infectious disease and cancer. Having steered clients through the preclinical studies to get them in front of the FDA for their pre-INS/BLA meetings, I have some concerns about the speed at which the current vaccines are purportedly being developed. The reason for this is that the FDA requires certain criteria to be met that simply cannot be accelerated.
There is a lot of discussion around DNA and RNA vaccines, none of which have been approved for use at this time. In their guidance document, the FDA states: â€œCOVID-19 vaccine development may be accelerated based on knowledge gained from similar products manufactured with the same well-characterized platform technology, to the extent legally and scientifically permissible.â€ If the FDA follows its statements, vaccines like the one Moderna is testing should have a longer route to approval and licensing.
Project Warp Speed intends to have manufacturers produce millions of vaccine doses in parallel with their trials so they can rapidly disseminate it upon clearance. However, the FDA guidance states the following with respect to manufacturing: â€œValidation would typically include a sufficient number of commercial-scale batches that can be manufactured routinely, meeting predetermined in-process controls, critical process parameters, and lot release specifications. Typically, data on the manufacture of at least three commercial-scale batches are sufficient to support the validation of the manufacturing process.â€ This is typical of any new drug. A commercial-scale usually implies hundreds of thousands of doses, each of which have to be tested to ensure they meet the design specifications.
Based on previous work with animal models used to test SARS-CoV-1 and MERS viruses, FDA is very concerned about the potential for enhanced respiratory disease (ERD). As is the case with any new pharmaceutical, the test population has to be very large and diverse in order to detect potential adverse reactions.
The FDA further specifies the following: â€œFDA encourages the inclusion of diverse populations in all phases of vaccine clinical development. This inclusion helps to ensure that vaccines are safe and effective for everyone in the indicated populations.â€ As you have pointed out, testing on something like a population of a million healthy Chinese soldiers in an area where the incidence of disease is low will not tell you if it is an efficacious vaccine. In addition to the various age groups with no co-morbidities, the vaccine must be tested on those with co-morbidities and also those who may have had previous virus exposure. They state it would be impractical to widely disseminate a vaccine and test for past exposure, so certainly some getting the vaccine will be positive for past exposure. As Paul Offit has previously stated, to achieve the numbers required on these diverse populations requires enormous numbers of test subjects, something that I believe is not achievable in a few months.
Something else that disturbs me regards preclinical toxicity testing of new, unproven types of vaccine candidates, i.e. those based on DNA or RNA expression. In the guidance, the FDA states, â€œFor a COVID-19 vaccine candidate consisting of a novel product type and for which no prior nonclinical and clinical data are available, nonclinical safety studies will be required prior to proceeding to FIH clinical trials 21 CFR 312.23(a)(8). Minimally, a safety study consists of exposing two animal species, usually rats and dogs, to the drug/vaccine at both the intended dose and 10-100 times the intended dose and monitoring them for at least three months. Each animal is subjected to an analysis of its hematology, blood chemistry, and other physiological and biochemical criteria. At the end, the animals are euthanized and a histological examination of 45 different tissues per animal must be performed. So when potential manufacturers like Moderna and others say their vaccine showed no toxicity, what did they actually do? A tox study takes months, and if they started it in January, they would just now be getting to a Phase 1 trial.
My fear is that weâ€™ll rush to market with vaccines that are either unproven in their efficacy, defined as providing protection from either infection or disease, or some of which may have adverse effects such as ARDs. Like Paul Offit, I fear our scientifically illiterate president may try to force release of a vaccine before it has been thoroughly tested in order to facilitate his chances of being reelected. This would give more ammunition to the anti-vaxx groups which are already grousing about being forced to get vaccinated.
Keep up the good work. Your podcast is truly one of the best (and healthiest) things on the internet.
Tom Kelly says
Mike Olive, You have the mind-set of Western Culture, Take the slow cautious approach “Law-suite awarenesses” approach to solve a medical problem. The Chinese Approach is Solve the problem at any cost. Do the Chinese have lawyers who would sue the State ?