City from Below

FIVE FACTOR TEST- FOUNDATION OF THE JACOBSON V MASSACHUSETTS DECISION

 

 

In Jacobson, the Court held  the common belief of the people was one of five determining factors.   According to Justice Harlan, the Court took judicial notice that people commonly believed the smallpox vaccine was preventive of smallpox, therefore the legislative decision to invoke police power was reasonable.

 

 

 

The common belief, is that it [the smallpox vaccine] has a decided tendency to prevent the spread of this fearful disease, and to render it less dangerous to those who contract it. While not accepted by all, it is accepted by the mass of the people, as well as by most members of the medical profession. It has been general in our state, and in most civilized nations for generations. It is generally accepted in theory, and generally applied in practice, both by the voluntary action of the people, and in obedience to the command of law...the legislature has the right to pass laws which, according to the common belief of the people, are adapted to prevent the spread of contagious diseases.

While we do not decide, and cannot decide, that vaccination is a preventive of smallpox, we take judicial notice of the fact that this is the common belief of the people of the state, and, with this fact as a foundation, we hold that the statute in question is a health law, enacted in a reasonable and proper exercise of the police power.' ​

The foundational question before the Court today would be whether an experimental genetic therapy, never before deployed nor subjected to any long term safety trials could be reasonably viewed as preventive of Covid 19.

In addition to FACTOR # 2, The Common Belief Test, the factors set forth by the Court for holding the statute in question was a health law enacted pursuant to the reasonable and proper exercise of police power was that the smallpox vaccine was:

FACTOR #1) Accepted by most members of the medical profession

FACTOR #2) Accepted by the mass of people

FACTOR #3) In general [use] in our state, and in most civilized nations for generations for nearly a century;

FACTOR #4) Generally accepted in theory

FACTOR #5) Generally applied in practice, both by the voluntary action of people, and in obedience to the command of law

Therefore, consistent with the holding in Jacobson, analysis of the reasonableness of any statute mandating a COVID experimental genetic therapy as a proper exercise of police powers, must focus on the 5  FACTORS the Court found dispositive.

 

MRNA IS A NOVEL AND UNPRECEDENTED GENE THERAPY AND SHOULD BE DISTINGUISHED FROM A 100 YEAR

OLD VACCINE. mRNA HAS NEVER BEEN IN GENERAL USE (FACTOR #3), HAS NEVER BEEN GENERALLY APPLIED IN PRACTICE (FACTOR #5) AND CANNOT HAVE BEEN ACCEPTED BY THE MASS OF PEOPLE, SINCE THE MASS OF PEOPLE HAVE NO REASONABLE BASIS FOR THAT ACCEPTANCE (FACTOR #2).  WHILE mRNA FAILS THE JACOBSON TEST BASED ON ITS NON COMPLIANCE WITH THE MAJORITY OF THE FACTORS SET FORTH BY THE COURT, TO COMPLETE THE ANALYSIS WE NOW TURN OUR ATTENTION TO THE REMAINING TWO FACTORS:

 

 

FACTOR # 4: GENERALLY ACCEPTED IN THEORY:

In order to determine if an mRNA genetic therapy is generally accepted in theory as safe and effective, we turn

to key excepts of Moderna's  8K Securities Exchange Commission Filing.

The following quotes are taken directly from that filing:

Currently, mRNA is considered a gene therapy product by the FDA. In certain countries, mRNA therapies have

not yet been classified or any such classification is not known to us.

mRNA drug development has substantial clinical development and regulatory risks due to the novel and unprecedented nature of this new category of medicines.

There have been few approvals of gene therapy products in the United States or foreign jurisdictions, and there have been well-reported significant adverse events associated with their testing and use.

Our mRNA development candidates and investigational medicines are based on novel technologies and any development candidates and investigational medicines we develop may be complex and difficult to manufacture. We may encounter difficulties in manufacturing, product release, shelf life, testing, storage, and supply chain management or shipping. 

We are utilizing a number of raw materials and excipients that are either new to the pharmaceutical industry or

are being employed in a novel manner. 

As a potential new category of medicines, no mRNA medicines have been approved to date by the FDA or other regulatory agency. Successful discovery and development of mRNA medicines by either us or our strategic collaborators is highly uncertain and depends on numerous factors, many of which are beyond our or their control.

The number and design of the clinical and preclinical studies required for the approval of these types of

medicines have not been established, may be different from those required for gene therapy products or may require safety testing like gene therapy products. Moreover, the length of time necessary to complete clinical

trials and to submit an application for marketing approval for a final decision by a regulatory authority varies significantly from one pharmaceutical product to the next, and may be difficult to predict.

In addition, the biology risk across the majority of our pipeline represents targets and pathways not clinically validated by one or more approved drugs. Only our H10N8 vaccine (mRNA-1440), H7N9 vaccine (mRNA-1851), phenylketonuria, or PKU, (mRNA-3283), and Fabry disease (mRNA-3630) programs pursue pathways where an approved pharmaceutical product has validated the vaccine and therapeutic intervention points. While we

believe we have made progress in seeking to reduce biology risk in certain settings, such as for vaccine targets for which we and others have shown the utility of neutralizing antibodies, the risk that the targets or pathways

that we have selected may not be effective will continue to apply across the majority of our current and future programs.

Gene therapies and mRNA based medicines may activate one or more immune responses against any and all components of the drug product (e.g., the mRNA or the delivery vehicle, such as a lipid nanoparticle) as well as against the encoded protein, giving rise to potential immune reaction related adverse events.

We must also complete extensive work on Chemistry, Manufacturing, and Controls, or CMC, activities (including yield, purity and stability data) to be included in the IND filing. CMC activities for a new category of medicines such as mRNA require extensive manufacturing processes and analytical development, which is uncertain and lengthy...As a result, we cannot be sure that we will be able to submit INDs or similar applications for our preclinical programs on the timelines we expect, if at all, and we cannot be sure that submission of INDs or

similar applications will result in the FDA or other regulatory authorities allowing clinical trials to begin.

The manufacturing processes for our development candidates and investigational medicines are novel and complex. There are no mRNA medicines commercialized to date or manufactured at such scale. Due to the novel nature of this technology and limited experience at larger scale production, we may encounter difficulties in manufacturing, product release, shelf life, testing, storage and supply chain management, or shipping. These difficulties could be due to any number of reasons including, but not limited to, complexities of producing

batches at larger scale, equipment failure, choice and quality of raw materials and excipients, analytical testing technology, and product instability

The process to generate mRNA investigational medicines encapsulated in LNPs is complex and, if not developed and manufactured under well-controlled conditions, can adversely impact pharmacological activity. Furthermore, we have not manufactured mRNA medicines at commercial scale. We may encounter difficulties in scaling up

our manufacturing process, thereby potentially impacting clinical and commercial supply.

Our investigational medicines may have undesirable side effects, such as the immunogenicity of the LNPs or

their components, the immunogenicity of the protein made by the mRNA, or degradation products, any of which could lead to serious adverse events, or SAEs, or other unexpected characteristics.

Although our mRNA development candidates and investigational medicines are designed not to make any permanent changes to cell DNA, regulatory agencies or others could believe that adverse effects of gene therapies products caused by introducing new DNA and irreversibly changing the DNA in a cell could also be a risk for our mRNA investigational therapies

There is typically an extremely high rate of attrition for product candidates across categories of medicines proceeding through clinical trials. These product candidates may fail to show the desired safety and efficacy profile in later stages of clinical trials despite having progressed through nonclinical studies and initial clinical trials. A number of companies in the biopharmaceutical industry have suffered significant setbacks in

later-stage clinical trials due to lack of efficacy or unacceptable safety profiles, notwithstanding promising

results in earlier trials

Most of our investigational medicines are formulated and administered in an LNP which may lead to systemic side effects related to the components of the LNP which may not have ever been tested in humans. While we have continued to optimize our LNPs, there can be no assurance that our LNPs will not have undesired effects. Our LNPs could contribute,

in whole or in part, to one or more of the following: immune reactions, infusion reactions, complement reactions,

opsonation reactions, antibody reactions including IgA, IgM, IgE or IgG or some combination thereof, or reactions to the PEG from some lipids or PEG otherwise associated with the LNP. Certain aspects of our investigational medicines may induce immune reactions from either the mRNA or the lipid as well as adverse reactions within liver pathways or degradation of the mRNA or the LNP, any of which could lead to significant adverse events in one or more of our clinical trials. Many of these types of side effects have been seen for legacy LNPs. There may be resulting uncertainty as to the underlying cause of any such adverse event, which would make it difficult to accurately predict side effects in future clinical trials and would result in significant delays in our programs.

In addition to serious adverse events or side effects caused by any of our investigational medicines, the administration process or related procedures also can cause undesirable side effects.

To date, our investigational medicines including RSV vaccine (mRNA-1777), CMV vaccine (mRNA-1647), hMPV+PIV3 vaccine (mRNA-1653), H10N8 vaccine (mRNA-1440), H7N9 vaccine (mRNA-1851), Zika vaccine (mRNA-1325), Chikungunya vaccine (mRNA-1388), PCV (mRNA-4157), OX40L (mRNA-2416), and VEGF-A (AZD8601) have been 

tested in fewer than 1,000 subjects in the aggregate

Our product and product intermediates are extremely temperature sensitive, and we may learn that any or all of our products are less stable than desired. 

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FACTOR # 1: ACCEPTANCE BY THE MEDICAL PROFESSION  

"You can't spend your time figuring out is it going to work or not going to work, you just have to commit." AstraZeneca CEO Pascal Soriot

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"COVID-19 vaccines under development are not guaranteed to work and people who say to expect a vaccine before year-end are doing a 'grave disservice to the public" 

 

Ken Frazier, July 13, 2020, CEO Merck. Interview published Harvard Business School website. 

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Col. Nelson Michael, director of the U.S. Army's Center for Infectious Disease Research who is working on the government's "Warp Speed" project to deliver a vaccine at scale by January, said companies usually have years

to figure this stuff out. "Now, they have weeks."

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This is the biggest logistical challenge the world has ever faced," said Toby Peters, an engineering and

technology expert at Britain's Birmingham university. "We could be looking at vaccinating 60% of the population."

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J&J has partnered with the U.S. government on a $1 billion investment to speed development and production

of its vaccine, even before it's proven to work. Never in history has so much vaccine been developed at the

same time - so that capacity doesn't exist," said Paul Stoffels, J&J's chief scientific officer, who sees filling

capacity as the main limiting factor.

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The speed of pre-clinical development for COVID-19 vaccines has been unprecedented — Moderna’s

innovative m-RNA platform moved from receiving the coronavirus genome to having a testable vaccine in 44 days.But as Dr. Fauci emphasized, even if everything goes perfectly during clinical trials, there are another 6-12 months to go until approval, and additional time will be needed to ramp up production.

Dr Joel M. Zinberg is a senior fellow with the Competitive Enterprise Institute in Washington, D.C. He is also

an associate clinical professor of surgery at the Mount Sinai Icahn School of Medicine and was senior

economist and general counsel at the Council of Economic Advisers from 2017 to 2019.
https://www.usatoday.com/story/opinion/2020/06/03/coronavirus-vaccine-not-end-all-must-plan-reopening-without-column/5265918002/

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“A lot of optimism is swirling around a 12- to 18-month time frame, if everything goes perfectly,” Rick Bright,

the former head of the Biomedical Advanced Research and Development Authority, told lawmakers in May. “We’ve never seen everything go perfectly. I think it’s going to take longer than that.”

For example, said Offit, most vaccines work by triggering an immune response inside the body without

making a person sick. But for this novel coronavirus, scientists still haven't had time to adequately study the body's immune response to infection -- meaning we don't know whether an immune system response necessarily protects against a future infection.

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Dr. Paul Goepfert, professor of medicine at the University of Alabama at Birmingham (UAB) and an expert in vaccine design, said a vaccine by January would only be possible "if everything works out perfectly."
https://abcnews.go.com/Health/safe-coronavirus-vaccine-years-eve/story?id=70457112


The speed with which researchers and pharmaceutical companies have responded to the coronavirus epidemic has been described as "unprecedented" by Dr Jerome Kim, Director-General of the International Vaccine Institute.
https://www.weforum.org/agenda/2020/06/vaccine-development-barriers-coronavirus/

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Dr. Paul Goepfert, professor of medicine at the University of Alabama at Birmingham (UAB) and an expert in vaccine design,

said a vaccine by January would only be possible "if everything works out perfectly."
https://abcnews.go.com/Health/safe-coronavirus-vaccine-years-eve/story?id=70457112


The speed with which researchers and pharmaceutical companies have responded to the coronavirus epidemic has been described as "unprecedented" by Dr Jerome Kim, Director-General of the International Vaccine Institute.
https://www.weforum.org/agenda/2020/06/vaccine-development-barriers-coronavirus/

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The potential benefits are to have a vaccine against Covid-19 ready for general use as soon as possible. That

won’t happen for a year at least. That timeline, Lynch went on, is “insanely fast,” 

Holly Fernandez Lynch, assistant professor of medical ethics at the University of Pennsylvania

https://www.statnews.com/2020/03/11/researchers-rush-to-start-moderna-coronavirus-vaccine-trial-without-usual-animal-testing/

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