Summary

Cancer patients urgently need more effective treatments that are accessible to everyone. This year alone, an estimated 1.9 million people in the United States will receive new cancer diagnoses, and cancer will kill more than 600,000 Americans. Yet there are no targeted therapeutics for many cancers, and the treatments that do exist can be prohibitively scarce or expensive.

Repurposing existing drugs, especially off-patent generics, is the fastest way to develop new treatments. Hundreds of non-cancer generic drugs have already been tested by researchers and physicians in preclinical and clinical studies for cancer, some up to Phase II trials, and show intriguing promise. But due to a market failure, there is a lack of funding for clinical trials that evaluate generic drugs. This means that there isn’t conclusive evidence of the efficacy and safety of repurposed generics for treating cancer, and so cancer patients who desperately need more (and more affordable) treatment options are unable to realize the benefits that existing generics might offer.

To quickly and affordably improve the lives of cancer patients, the Biden-Harris Administration should create the Repurposing Generics Grant Program through the National Cancer Institute. This program would fund definitive clinical trials evaluating repurposed generic drugs for cancer. A key first step would be for President Biden to include this program in his FY2022 budget proposal. Congress could then authorize the program and related appropriations totaling $100 million over 5 years.

Introduction

For those who can afford to fill their fridge by clicking a button on their smartphone or walking around to the organic grocery around the corner, it is easy to forget how complex and fragile our food systems can be. However, for millions of Americans who suffer from poor health because of food insecurity, or farmers and ranchers whose yields are decreasing along with the nutrient density of their product, that fragility is felt every day. Sustainable food systems engender intricate connections and feedback loops among climate change, public health, food security, national security, and social equity. When one of these factors is overstressed, disaster can result.

COVID-19 has underscored the vulnerability of our food systems. The pandemic caused restaurants to close overnight, strained supply chains, and led to food rotting on land, in warehouses, and on shelves. Low-income and food-insecure families waited in lines that stretched for miles while producers and distributors struggled to figure out how to get supplies to those who needed them. Concurrently, generations of racial inequity and the coordinated disenfranchisement of Black, Indigenous, and other people of color (BIPOC) has crystalized as an issue that needs to be addressed at every level in our country, especially within our food and agricultural systems.

Addressing these issues—now and for the future—requires a coordinated response across sectors. Food security is deeply intertwined with public health and social equity. Un- and under- employment, the racial wealth gap, and increased financial hardships for certain communities result in increased malnutrition, obesity, metabolic diseases, and chronic illness, as well as particular susceptibility to severe impacts from COVID-19 infections during the present pandemic. The climate crisis compounds these issues. Farming practices that degrade soil health, reduce agriculture capacity, and compromise the well-being of small farms and rural communities prevent us as a nation from becoming healthier and more secure. As we look at opportunities to “build back better,” we must embrace paradigmatic shifts—fundamental restructuring of our systems that will support equitable and inclusive futures. Compounding crises require changes in not only what we do, but how we think about what we do.

A fundamental problem is that progress in modern agriculture has been implicitly defined as progress in agricultural technology (AgTech) and biotechnology. Little emphasis is placed on examining whole-systems dependencies and on how connections among soil health, gut bacteria, and antibiotic use in livestock impact human health, economic prosperity, and climate change. With such a narrow view of “innovation,” current practices will solve a handful of isolated problems but create many more.

Fortunately, alternatives are ripe for adoption. Regenerative farming, for instance, is a proven way to combat future warming while increasing the adaptive capacity of our lands, providing equitable access to food, and creating viable rural economies. Regenerative farming can also restore soil health, which in turn improves food quality while enhancing carbon sequestration and providing natural water treatment.

Transitioning away from dominant but harmful practices is not easy. The shift will require an inclusive innovation ecosystem, investors with long time horizons, new infrastructure, tailored education, economic incentives, and community safety nets. This document explores how the agricultural sector can support, and be supported by, policies that advance science, technology, and innovation while revitalizing living systems and equitable futures. We recognize that agricultural policy often overlooks interventions that are appropriately suited to advance these concepts with Black, Indigenous, people of color (BIPOC) communities and on tribal lands. To avoid this mistake, the concepts presented herein start from the ground up. We focus on the benefits of improving soil health and food security through regenerative agricultural activities, and provide examples of policies that could promote such activities in a variety of ways. Letting practice drive policy— instead of having policy dictate practice—will result in more sustainable, inclusive outcomes for all communities.

While agricultural policy can and should be shaped at the local, regional, state, and national level, this document places special emphasis on the role of the federal government. Building better food systems will require multiple government agencies, especially federal agencies, to collaboratively advance more equitable policies and practices. Most national agricultural programs are housed within the U.S. Department of Agriculture (USDA). But the interconnectedness of how we produce food and fiber (and the ways in which those practices impact our environment and nourish people) demands priority investment not only from USDA, but also from the Environmental Protection Agency, the Department of Energy, the Department of the Interior, the Department of Defense, and the Department of Health and Human Services—to name just a few. This document—based on a review of existing policy recommendations and current practice, development and refinement of new ideas, and identification of underleveraged roles and programs within the government— suggests what such investments might look like in practice.

As the U.S. continues to grapple with the pandemic, there are growing concerns about the risks posed by variants of SARS-CoV-2 – the coronavirus that causes COVID-19. Recent data have shown that at least one SARS-CoV-2 variant is more transmissible than the original, and there are questions as to whether any variants could be more deadly. The main way to detect emerging variants is to perform widespread genome sequencing, but the sequencing infrastructure in the U.S. is struggling to keep up with demand. This issue was a major focus of the Centers for Disease Control and Prevention’s (CDC) briefing to the House Appropriations Subcommittee on Labor, Health and Human Services, Education and Related Agencies this week.

Origin of variants and their detection

Viruses replicate by taking advantage of a person’s own cells, and each replication introduces small changes into a virus’ genetic code. Usually, these mistakes either have no impact, or are harmful to the virus. Sometimes, though, these errors give the virus an advantage, like increased ability to infect other people. Besides increased transmissibility, it is possible that variants could also cause more severe disease, evade detection by diagnostic tests, reduce the effectiveness of treatments, escape infection-induced immunity, or render vaccines less effective.

These risks are why it is imperative that public health officials track the emergence of variants around the country, and around the globe. Variants are found by extracting genetic material from patient samples, using sequencing equipment to read the virus’ genetic code, and comparing it with other known samples. When increasing numbers of cases of disease are found to have been caused by a virus with a genetic signature that is only slightly different from that of the known samples, scientists can estimate that they may have found a new variant. For SARS-CoV-2 specifically, there are a few variants that appear to have an advantage and are able to spread much more easily than the original strain. These variants include the UK and South African strains. There are also some early data that a variant discovered in California is more contagious than the original.

Challenges for genome sequencing of viruses in the U.S.

Public health officials use genomic sequencing to monitor for a variety of viruses, but the increased demand during the COVID-19 pandemic has put the U.S.’ sequencing infrastructure under strain. Though the U.S. has over 28 million COVID-19 cases, or about one-fourth of the total number of cases in the world, only about 96,000 samples, or around 0.3 percent, have been sequenced. For U.S. labs, the sequencing process can be costly and time-consuming, taking 48 hours to readout a virus’ genome in the best case scenario, though typical turnaround times stretch up to seven days. The cost of just one virus genome sequence can be anywhere from $80 to $500.

The country’s current genomic sequencing infrastructure has not been prioritized as a public health need and, in the past, sequencing was typically performed only by research universities. In 2014, the CDC started funding public health labs to track foodborne illnesses with genomic sequencing. By 2017 every state had labs which could perform genome sequencing, but obtaining funding is still difficult.

Current efforts and the road ahead

The CDC has been working to form various partnerships to boost the U.S.’ capacity for virus genome sequencing. According to its website, CDC has focused on several activities to increase genomic sequencing capacity, including:

• Leading the National SARS-CoV-2 Strain Surveillance (NS3) system;
• Partnering with commercial diagnostic laboratories;
• Collaborating with universities;
• Supporting state, territorial, local, and tribal health departments; and
• Leading the SARS-CoV-2 Sequencing for Public Health Emergency Response, Epidemiology, and Surveillance (SPHERES) consortium.

CDC Director Rochelle Walensky echoed this during Tuesday’s briefing and noted that under her leadership, the agency has scaled from 250 SARS-CoV-2 sequences per week to 14,000 per week. She hopes to scale up enough that the CDC can sequence 25,000 samples per week, which is close to about 5% of positive cases. To do this, the White House announced last week it would provide $200 million to support more genomic sequencing, and the U.S. Congress is considering adding almost $2 billion to that effort in the next economic relief package.

This funding is also intended to sustain the U.S.’ genomic sequencing infrastructure for the future. Senator Tammy Baldwin (D-WI), who introduced the legislation to support further sequencing, said the federal government should establish “the basis of a permanent infrastructure that would allow us not only to do surveillance for COVID-19, to be on the leading edge of discovering new variants, but also…have that capacity for other diseases.” During Tuesday’s briefing, Ranking Member Tom Cole (R-OK) affirmed this idea, saying that the House Appropriations Committee needs to think about establishing long-term funding streams to ensure that infrastructure developed during this crisis can last well in the future.

The COVID-19 pandemic has highlighted gaps in U.S. infrastructure for the genomic sequencing of pathogens, and the importance of tracking virus variants for our public health. While the CDC works with its partners to rapidly scale up sequencing capacity, lawmakers need to consider how to sustain it for future outbreaks. As the Biden Administration and Congress consider scaling and sustainment, we encourage the CSPI community to serve as a resource to federal officials on this topic.

Given the pervasiveness of COVID-19 throughout the U.S., the risk of infection to transportation workers and passengers is significant. For instance, in a survey of over 600 bus and subway workers in New York City, almost one quarter reported contracting COVID-19, and 76 percent personally knew a coworker who had died from the disease. During last week’s hearing, the House Transportation and Infrastructure Committee discussed best practices for protecting transportation workers and passengers from COVID-19, with a particular focus on preventing the spread of the coronavirus through the air.

Transmission of COVID-19 via aerosols

In early October 2020, the Centers for Disease Control and Prevention (CDC) updated its guidance, confirming that COVID-19 can be transmitted via aerosols in addition to larger respiratory droplets. When an individual with COVID-19 coughs, speaks, or breathes, tiny coronavirus-carrying droplets can travel over distances longer than six feet and stay suspended in the air for up to several hours. For the coronavirus, most transmission via aerosols occurs in enclosed, poorly ventilated spaces, when a person is exposed to respiratory particles for an extended period of time. Mass transit vehicles can be one such pathway for infection since people from different households share the same spaces while either working or riding to their destinations.

Protecting people from COVID-19 involves implementing measures to keep virus particles from entering individuals’ noses and mouths. Scientists have found that wearing a face covering can limit the amount of droplets an individual releases, and thus also reduce the amount of virus particles in the air. Masks can also provide some degree of protection to the wearer by providing a barrier between coronavirus-carrying droplets and the person’s nose and mouth. The CDC also suggests that buildings and transportation systems examine the quality of their ventilation and filtration systems to reduce spread of COVID-19. Effective ventilation quickly dilutes the amount of virus particles in the air and allows clean air to quickly circulate in enclosed spaces. Advanced filtration systems can help catch and retain virus-carrying particles on tightly woven inserts, keeping them from reentering the space. While any one of these methods alone is not sufficient to protect people from the coronavirus, a layered approach that combines many safeguards can reduce the ability of respiratory diseases like COVID-19 to spread.

Using advanced filters to remove coronavirus-carrying particles from enclosed spaces

Several Members of the Committee noted the importance of developing and implementing advanced filtration technologies on transportation systems and in buildings. Scientists estimate that the coronavirus can spread even via airborne particles under 5 microns in diameter. (For comparison, a single raindrop is typically about 2,000 microns in diameter.) Most buildings have filters with a Minimum Efficiency Reporting Value (MERV) rating of between 7 and 8, which means they can filter up to 84.9 percent of particles between 3 and 10 microns in diameter. Subway cars also use these filters. The highest rated filters (MERV 16 to 20) can capture over 75 percent of particles that are between 0.3 and 1 micron in diameter, and high efficiency particulate air (HEPA) filters, which are used on airplanes, can theoretically remove at least 99.97 percent of particles 0.3 microns in diameter and larger. To better protect workers and passengers, transportation systems like Washington, DC’s Metro and the Bay Area Transit system in San Francisco are already testing out more advanced filtration technologies through pilot programs funded by the Federal Transit Administration.

Benefits of advanced filters beyond reducing spread of COVID-19

Widespread adoption of advanced filtration technologies can be beneficial not only to reduce the amount of coronavirus-carrying particles in the air, but also to trap other harmful aerosols. During the hearing, Dr. David Michaels from George Washington University and Dr. William Bahnfleth from Penn State University both noted that investing in better filters now can also protect people from inhaling harmful particulate matter from other sources. For example, wildfires contribute about 30% of all fine particulate emissions in the U.S., with many of these being 2.5 microns or smaller. Inhaling these harmful particles can be associated with cardiovascular and respiratory issues, as well as premature mortality, particularly in vulnerable groups such as the elderly, children, and pregnant women.

Enhanced air filtration is a useful tool to help slow the spread of COVID-19, especially when used alongside other measures like wearing masks, improving ventilation, social distancing, and hand washing. As the new administration and Congress work toward ending the pandemic, practices such as the widespread adoption of more robust filters are likely to be examined in more detail. We encourage our community to get involved in the effort to counter COVID-19 by engaging in future congressional hearings through our Calls to Action.

Summary

The coronavirus pandemic has forced a sudden acceleration of a prior trend toward the virtual provision of healthcare, also known as telemedicine. This acceleration was necessary in the short term so that provision of non-urgent health services could continue despite lockdowns and self- isolation. Federal and state policymakers have supported the shift toward telemedicine through temporary adjustments to health benefits, reimbursements, and licensure restrictions.

Yet if policymakers direct their attention too narrowly on expanding telemedicine they risk missing a larger—and as yet mostly unrealized—opportunity to improve healthcare in the United States: increasing the overall share of health services provided directly to the home. At-home healthcare includes not only telemedicine, but also medical house calls (home-based primary care) as well as models in which individuals within communities offer simple support services to one another (i.e., the “village” model of senior care, which could be extended to included peer- to-peer health service delivery). The advent of “exponential” technologies such as artificial intelligence (AI), blockchain, and the Internet of Things (IoT) is unlocking new possibilities for at- home healthcare across each of these models.

The next administration should act to reduce four types of barriers currently preventing at-home healthcare from reaching its full potential:

1. Labor-market barriers (e.g., unnecessarily restrictive scope-of-practice rules and requirements for licensing and certification)
2. Technical barriers (e.g., excessively slow and burdensome processes for regulatory approval, weak or absent standards for interoperability)
3. Financial/regulatory barriers (e.g., methodologies for determining eligibility for reimbursements that favor incumbents over innovators)
4. Data sharing / interoperability barriers (e.g., overly restrictive constraints related to data privacy and portability)

The COVID-19 pandemic has highlighted the urgent need to address lags in American pharmaceutical manufacturing. An investment of $5 billion over five years will improve U.S. pharmaceutical manufacturing infrastructure, including the development of new technologies that will enable the responsive, end-to-end, on-demand production of up to half of the Food and Drug Administration (FDA) list of 223 essential medicines by year two, and the entire portfolio by year five. Spearheading improvements in domestic manufacturing capacity, coupled with driving the advancement of new adaptive, on-demand, and other advanced medicine production technologies will ensure a safe, responsive, reliable, and affordable supply of quality medicines, improving access for all citizens, including vulnerable populations living in underserved urban communities, rural areas, and tribal territories.

Challenge and Opportunity

Urgent Need to Strengthen U.S. Pharmaceutical Manufacturing

COVID-19 has served as a wake-up call and an opportunity to bring pharmaceutical manufacturing into the 21st century. Production factory closures, shipping delays, shutdowns, trade limitations, and export bans have severely disrupted the supply chain. Yet the demand for vaccines and COVID-19 treatment options worldwide continues to increase. However, recent advances in manufacturing technology can be deployed to create a 21st century domestic pharmaceutical manufacturing economy that is distributed, flexible, and scalable, while producing consistent high-quality medicines that Americans rely on.

To improve national security and achieve the goal of medicine production self-sufficiency, the Biden-Harris Administration has an opportunity to address legacy issues plaguing the pharmaceutical manufacturing industry and usher in a technology revolution that will leapfrog our legacy 19th century industrial manufacturing processes. The Biden-Harris Administration should prioritize:

Improving the domestic production of small-molecule medicines, including Key Starting Materials (KSMs) and Active Pharmaceutical Ingredients (APIs) in order to reduce dependence on foreign manufacturers. China and India together supply 75- 80 percent of the APIs imported to the U.S.¹ In March, during the largest spring spike in U.S. COVID-19 cases, India restricted the export of 26 APIs as well as finished pharmaceuticals. The U.S is the leading market for generic pharmaceuticals, with 9 out of every 10 prescriptions filled being for generic drugs in 2019, and a projected market value of $415 billion by 2023.² An aggressive race to the bottom in terms of price has driven the vast majority of supply chain manufacturing overseas, where lower production costs and government subsidies, particularly for exports, benefit foreign suppliers.

Improving the scale, efficiency, and effectiveness of domestic biopharmaceutical manufacturing. The past decade has ushered in a significant shift in the nature of pharmaceutical products: there is now a greater prevalence of large molecule drugs, personalized therapeutics, and a rise in treatments for orphan diseases. New approaches to developing vaccines, such as the mRNA COVID-19 vaccine, are setting a new paradigm for future vaccines using DNA, RNA, adenoviruses, and proteins. There is an urgent need to scale up the domestic manufacturing of biologics, including vaccines, to address biomedical threats. In addition, innovation in manufacturing technology is critical to improving both scalability and time to market. New technology will improve yields while lowering costs and reduce waste through green chemistry.

Additional benefits associated with establishing a robust domestic manufacturing base, including distributed manufacturing capability, include:

Reducing vulnerabilities associated with an over-reliance on centralized manufacturing and processing models. In the food industry, a COVID-19 outbreak in just a few chicken and pork processing plants led to a nationwide shortage of these important foods. A more flexible, resilient distributed manufacturing model, such as one utilizing additive manufacturing and 3-D printing, would have prevented the need for such a disruptive response. 3-D printing, for example, has successfully delivered more than 1,000 parts to local hospitals during the pandemic.

Improving the reliability of facilities and the quality of products for the U.S. market through the development and deployment of advanced manufacturing technologies. Low-cost, offshore manufacturing raises quality risks; more than half of FDA warning letters issued between 2018 and 2019 were sent to facilities in India or China.4 There are numerous examples of risks to both the health and security of U.S. citizens in the recent past. In 2007, a Chinese company deliberately contaminated the blood thinner Heparin and 246 Americans died. In 2015, the FDA banned 29 products after inspecting a Chinese pharmaceutical factory, although it exempted 14 products over U.S. shortage concerns. And in 2018, a Chinese vaccine maker sold at least 250,000 substandard doses of vaccine for diphtheria, tetanus, and whooping cough.

Improving access for vulnerable populations living in underserved urban communities, rural areas, and tribal territories. COVID-19 created unprecedented pressure on the federal system when requests from 56 State, Local, Tribal, and Territorial (SLTT) authorities nearly simultaneously requested medical supplies. According to testimony presented by the RAND Corporation, the quantities of material in the Strategic National Stockpile (SNS) were not nearly enough to fill all of the requests, resulting in a heated competition and a failure to deliver products to all of the different parts of the United States equitably.

Reducing critical drug shortages that have plagued U.S. health systems for more than a decade. With COVID-19 cases on the rise, and hospitalizations increasing in more than 40 states, critical drug supplies are waning, with 29 out of 40 drugs used to combat the coronavirus currently in short supply. In addition, 43% of 156 acute care medicines used to treat various illnesses are running low. In 2019 the U.S. experienced 186 new drug shortages; 82% of which were classified as being due to “unknown” reasons, largely because of the intentional opacity and secrecy of the upstream supply chain. According to the Center for Infectious Disease Research and Policy (CIDRAP) the U.S. health system spends more than $500 million a year on estimated costs related to drug shortages, with approximately $200 million in direct costs and up to $360 million on indirect costs.

Stabilize pricing by enabling ‘just in time’ manufacturing capability that reduces the need to stockpile large supplies of medicines and is more responsive to surges in demand. Furthermore, complex supply chains, procurement mechanisms, and the consolidation of U.S. buyers create ‘pay-to-play’ schemes that contribute to chronic drug shortages by driving manufacturers out of the market and contribute to price volatility. New technologies that enable responsive and efficient approaches to surges in demand, or to address drug shortages, will also stabilize pricing over time. Today, one in four Americans cannot afford their medication. Mylan, for example, increased the price of EpiPen by more than 500%, from $94 for a two-dose pack in 2007 to $608 in 2018.

21st Century Problems Require 21st Century Solutions

Advanced manufacturing technologies such as continuous flow, which allows for drugs to be produced in a continuous stream, can reduce the time it takes to manufacture a drug and ensure quality through advanced controls and process analytic technologies. These technologies can enable remote monitoring during production and real-time release testing. In addition, miniaturized manufacturing units that could easily fit in existing pharmacies would facilitate a distributed network for producing medicines that is flexible enough to rapidly pivot and make any therapeutic required for national security or emergency preparedness with short lead times. A distributed network of on-demand pharmaceutical manufacturing devices will improve supply availability without the need to stockpile large quantities of medications.

Automation will play a key role in advanced pharmaceutical manufacturing, as will 3-D printing. Automation will reduce manufacturing overheads and ensure quality, scalability, and increased outputs. It allows advanced connectivity of equipment, people, processes, services, and supply chains. The 3-D printing of pharmaceutical products, meanwhile, is accelerating following the FDA’s approval of the first 3-D printed drug in 2015. This technology accommodates personalized doses and dosage forms and other emerging technologies that enable bespoke tablet sizes, dosages, and forms (suspension, wafers, gel strips, etc.) to optimize patient compliance and ease of use. Another major advantage is the possibility of redistributed manufacturing–printing medicine much closer to the patient. 3-D printing and on-the-spot drug fabrication will have major implications in medical countermeasures and for medications with limited shelf-life.

Finally, investing in advanced biopharmaceutical manufacturing infrastructure and innovation would establish the capacity to produce domestically through a network of high-tech, end-to-end manufacturing and development solutions, which will ensure that the medicines of today and tomorrow, such as new vaccines, can be made quickly, safely, and at scale.

Plan of Action

The Biden-Harris Administration should launch a national adaptive pharmaceutical manufacturing initiative focused on the ambitious goal of achieving medicine production self-sufficiency. The Presidential Initiative should be led by an Ambassador who reports to the Secretary of Defense. The Secretary of Defense is already leading a whole-of-government effort to assess risk, identify impacts, and propose recommendations in support of a healthy manufacturing and defense industrial base – a critical aspect of economic and national security. The Department of Defense (DoD) coordinates these efforts in partnership with the Departments of Commerce, Labor, Energy, and Homeland Security, and in consultation with the Department of the Interior, the Department of Health and Human Services (HHS), the Director of the Office of Management and Budget, and the Director of National Intelligence.

Clear deliverables and timeline-dependent milestones are critical to the success of this initiative. New local manufacturing solutions — such as state-of-the-art facilities and devices for automated end-to-end pharmaceuticals to be deployed in a trailer — can augment ongoing efforts to reduce manufacturing ramp-up time, the need for strict environmentally controlled secure storage facilities, and waste from expired medications. Having stand-alone or mobile devices for automated end-to-end pharmaceuticals would empower local authorities to manage delivery and distribution protocols, ensuring that local populations have the lifesaving medicines they need when they need them.

To this end, the DoD, in collaboration with HHS and the FDA, should launch a national initiative to increase U.S. manufacturing capacity and accelerate the development of new technology, with an emphasis on the adoption of advanced analytical capabilities to ensure quality. These platforms should be able to produce precursors, APIs, and final drug products (small molecule and biologics) in multiple forms, enabling rapid response priority medicines on demand, targeting the creation of a self-sustaining domestic supply chain of the 223 medicines on the FDA Essential Medicines list, as well as new vaccines and medicines coming off patent in the next 5 years.

The establishment of a national pharmaceutical manufacturing network will facilitate a U.S. strategic asset that changes how we source, manufacture, and distribute medicines. This robust domestic network will mitigate drug shortages, ensure quality, and allow rapid response to emergency scenarios. Importantly, it re-establishes a domestic pharmaceutical manufacturing industry that relies less on overseas suppliers, advances our country’s innovation prowess, and will create thousands of new U.S. jobs.

Recommendations for the Department of Health and Human Services and the Department of Defense

To enable a more resilient, responsive and adaptive U.S. pharmaceutical supply chain and achieve medicine production self-sufficiency, the following actions are recommended.

First, sign an executive order that directs the formation of a Joint Interagency Task Force (JIATF) DoD, HHS and FDA, led by a Presidential appointee (Ambassador), with a $5 billion, 5-year funding commitment, to establish a more robust domestic responsiveness that includes advanced manufacturing technologies for biologics and small molecules. A key objective of the executive order and the formation of a JIATF is to ensure the U.S. can produce medicines stateside with improved responsiveness.

This initiative will:

• Identify a portfolio of products that can be rapidly deployed at a national, state or local level utilizing advanced manufacturing platforms, identify associated research and development agenda needs, and determine how this aligns with other initiatives such as the Strategic National Stockpile.
• Support targeted synthetic biology research and development to enable faster manufacturing of low-cost, on-demand vaccines and precision immunotherapies.
• Support the advanced development of green, modular, on-demand small-molecule manufacturing technologies that would accommodate small batch lines, with an ability to scale and produce higher volume when needed. • Support targeted advanced development of sensor technologies that can monitor online and real-time quality control.
• Support the acquisition and/or establishment of new U.S.-based manufacturing facilities.
• Support green technology solutions.
• Establish a center for excellence in advanced manufacturing at the FDA, to support and advance regulatory science.
• Identify new business models to support the economically sustainable domestic adoption and deployment of new manufacturing technology.
• Enact push and pull incentives to direct new medical countermeasure development funded by HHS (Biomedical Advanced Research and Development Authority, BARDA) and other federal agencies to utilize adaptive manufacturing practices as appropriate.

Key milestones and deliverables of this initiative include the following:

1. By year 2, ensure that 50% of the FDA’s Essential Medicines are manufactured from end-to-end in the United States, to include starting materials and APIs.
2. By Year 5, the FDA will have the capability to manufacture all Essential Medicines in the United States.
3. In this same time frame, the quality of every dose of the medicines produced can be provided to the FDA for oversight.
4. All starting materials are sourced domestically or from trusted allied nations.

Conclusion 

Expanding critical U.S. pharmaceutical manufacturing infrastructure and establishing an adaptive, transparent on-demand pharmaceutical manufacturing capability guarantees safe, secure, high-quality, and reliable supply of affordable drugs and would create thousands of new U.S. high-paying jobs. By utilizing green technology, it could reduce hazardous material waste by as much as 30 percent over conventional manufacturing. It would also improve transparency and supply chain efficiencies that could reduce shortages, lower costs, and improve the quality of medicines. A distributed, modular, on-demand manufacturing network capable of making biologics and small molecules cannot be disrupted by the loss of centralized facilities, natural disasters, pandemics, or adversarial actions. New local on-demand manufacturing solutions will reduce manufacturing ramp-up time, the need for strict environmentally-controlled secure storage facilities, and waste from expired medications. It will empower local authorities to manage delivery and distribution protocols, ensuring that local populations have the lifesaving medicines they need when they need them. In addition, it would offer the potential to improve warfighter resilience and recovery by providing the groundwork for producing medicines on demand, and at the point of care, whether it be on a C-5, submarine, or at a forward combat support hospital.

Summary

Prevention plays a crucial and underappreciated role in our health system. To improve health outcomes and bring down costs, it will be important to establish a better balance between preventive measures and drug treatments. The next administration should provide incentives to healthcare providers that scale up—and reduce costs of delivering—preventive interventions with demonstrated efficacy. Currently, the U.S. Department of Health and Human Services (HHS) sets broad standards regarding managed care contracts. But states have considerable latitude. States can set income eligibility criteria, define services, and set alternative payment methods with Managed Care Organizations (MCOs). And in just the last few decades, Medicaid programs have been almost fully privatized: MCOs now cover over 85% of the Medicaid population. Because of the existing patchwork of insurance programs and state rules, it is important that regulations set minimum national standards to ensure that health care is accessible and affordable for those who need it the most. Particularly important to this effort are non- distortionary prices and reimbursement policies.

For a few decades, policymakers have, with bi-partisan consensus, moved away from a fee-for-service (FFS) system whereby providers are paid for service delivery and toward capitation and pay for performance (p4p) models. While these models offer significant improvements over FFS models, each involves risks of incentivizing non-optimal care and expenditures if they are not structured carefully. When paying capitation rates, bonuses adjusting for population risk alone should be avoided as this incentivizes an increase in diagnoses without necessarily improving care. Either all health care payments should be p4p, or a p4p component should be added to the capitation base. Pharmacological interventions should also be included in the overall provider reimbursement structure to align reimbursement incentives with health outcomes. Healthcare providers will then determine the right mix of services. Furthermore, while p4p is generally a good idea (i.e., hospitals and MCOs are rewarded for decreasing the number of avoidable hospital readmissions), if this metric is not applied homogeneously across all services, this payment structure significantly hampers the provision of preventive services.

Summary

From HIPAA to doctor-patient confidentiality, the U.S. healthcare system is replete with provisions designed to ensure patient privacy. Most people are surprised, then, to hear that patients in the United States do not legally own nearly any of their health data: data as diverse as health and medical records, labs, x-rays, genetic information, and even physical specimens such as tissue and blood removed during a procedure.

Providing patients with agency over their health data is necessary for elevating patients as partners in their own health management—as individuals capable of making genuinely informed and even lifesaving decisions regarding treatment options.

The next administration should pursue a two-pronged approach to help do just that. First, the administration should launch a coordinated and comprehensive patient-education and public- awareness campaign. This campaign should designate patient data and tissue rights as a national public-health priority. Second, the administration should expand provisions in the Cures 2.0 Act to ensure that healthcare providers are equally invested in and educated about these critical patient issues. These steps will accelerate a needed shift within the U.S. healthcare system towards a culture that embraces patients as active participants in their own care, improve health- data literacy across diverse patient populations, and build momentum for broader legislative change and around complex and challenging issues of health information and privacy.

There has been a surge of public interest in the drug fluvoxamine as a potential treatment for individuals with mild COVID-19, and Congressional offices are receiving many questions about the possibility of using the drug to counter COVID-19 from constituents. This brief outlines what is known to date about fluvoxamine in the context of the coronavirus pandemic in order to help both policymakers and scientists discuss this issue with those in their communities.

Fluvoxamine is a long-used drug that showed promising preliminary results in a small, well-controlled COVID-19 patient study

The generic drug fluvoxamine (also referred to by the brand name Luvox) was first synthesized in 1971, and is used to treat anxiety, depression, and obsessive-compulsive disorder. Fluvoxamine blocks serotonin reuptake in the brain, but it is chemically unrelated to other selective serotonin reuptake inhibitors that are used to treat anxiety or depression, like fluoxetine (Prozac) or sertraline (Zoloft). Studies have demonstrated that fluvoxamine also binds a protein in mammalian cells called the sigma-1 receptor. One of this receptor’s functions is to regulate cytokine production; cytokines cause inflammation. When fluvoxamine has been used in the laboratory, it results in a dampened inflammatory response in human cells in the test tube, and protects mice from lethal septic shock, which is an out-of-control immune response to infection, causing massive inflammation that can impede blood flow to major organs, and result in organ failure. Notably, retrospective analyses have indicated that COVID-19 patients given antipsychotic drugs that target the sigma-1 receptor were less likely to require mechanical ventilation than COVID-19 patients given other antipsychotic drugs, and some drugs that bind the sigma-1 receptor also have antiviral activity against SARS-CoV-2 in the petri dish.

Researchers reasoned that fluvoxamine may be able to stave off the “cytokine storm” that can lead to the out-of-control inflammatory response that appears to cause severe respiratory and blood-clotting issues for some people infected with the coronavirus, and tested the drug in a pilot study to gauge whether it has potential as a treatment for COVID-19. The study was a small, double-blind, placebo-controlled, randomized clinical trial of 152 non-hospitalized adults with mild COVID-19. Treatment of symptomatic, confirmed COVID-19 patients started within 7 days of their diagnosis. None of the 80 patients treated with fluvoxamine experienced clinical deterioration, compared to 6 of 72 patients treated with placebo who experienced both “1) shortness of breath or hospitalization for shortness of breath or pneumonia and 2) oxygen saturation less than 92%.” While this amounted to a statistically significant difference, the study serves as only preliminary evidence for the efficacy of fluvoxamine as a therapy to counter COVID-19, and a much larger clinical trial has been initiated to pursue conclusive results.

Summary of the 152-participant fluvoxamine/COVID-19 clinical trial. Image source: The Journal of the American Medical Association

Further study of treating many more COVID-19 patients with fluvoxamine is required before the drug should be used outside of clinical trials as a therapy to counter COVID-19

While the double-blind, placebo-controlled, randomized design of the clinical trial does minimize bias and provide the opportunity to identify a causal relationship between treatment and patient outcome, larger randomized trials with more definitive metrics in place for assessing patients’ health status are necessary in order to reach a conclusion about whether fluvoxamine should be used to treat patients with COVID-19 outside of clinical trials. The findings of this single, small study are a launching point for larger clinical trials, and “should not be used as the basis for current treatment decisions.”

The limitations of the study include the small number of COVID-19 patients involved and the low number of patients in the placebo group whose conditions worsened – only six. And while fluvoxamine is safe, easily accessible, administered orally, and inexpensive, it may interact with other drugs, and does have some side effects, such as nausea, diarrhea, loss of appetite, increased sweating, dizziness, drowsiness, insomnia, or dry mouth.

The researchers who performed this pilot study are currently conducting a larger clinical trial to conclusively determine whether fluvoxamine is an advisable treatment for mild COVID-19. The trial is expected to be watched closely since the identification of drugs – in addition to the monoclonal antibody treatments developed by Regeneron and Eli Lilly – that could be used to reduce the likelihood of progression from mild to more severe COVID-19 would greatly improve health outcomes for people infected by the coronavirus, as well as reduce the burden on the US healthcare system.

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This briefing document was prepared by the Federation of American Scientists along with Professor Alban Gaultier at the University of Virginia and Professor David Boulware at the University of Minnesota.

Summary

While the Veterans Health Administration (VHA) provides telehealth services across the country, current services neglect to respond to the access challenges that constrain veterans, particularly in rural areas. Of the nearly 5 million veterans who live in rural areas, 45% lack access to reliable broadband internet and smart technology. In the absence of available or reliable internet, veterans are often forced to access telehealth services in person at VA Clinical Resource Hubs (CRHs). However, these facilities are limited in number and are typically located far from rural communities. To address digital inequities and constraints posed by infrastructure and geography, the VHA needs to create more ways for veterans to access and fully utilize telehealth. We propose that the VHA partner with federal agencies like the United States Postal Service (USPS) or United States Department of Agriculture (USDA), leveraging their infrastructure to develop telehealth hubs. We further suggest that the VHA develop and lead a federal taskforce to build critical technology infrastructure that will facilitate expansion and use of telehealth for veterans. These interventions will be vital for ensuring that veterans in rural communities have greater access to care and can not only survive but thrive.

Summary

Optimizing the dosing of many expensive drugs can drastically reduce both costs and toxicities. The Federal Government, state governments, employers, and individual patients could collectively save tens of billions of dollars each year by simply optimizing the dosing of the most expensive prescription drugs on the market, particularly in oncology. Optimized dosing can also improve health outcomes. The next administration should, therefore, launch an effort to control the cost of prescription drugs through an evidence-based approach to optimizing drug dosing and improving outcomes. The requisite trials pay for themselves in immediate cost savings.

Summary

As the United States continues to grapple with unprecedented economic, health, and social justice crises that have had a devastating and disproportionate effect on the very communities that have long struggled most, the next administration must act quickly to ensure equitable recovery. Improving economic mobility and increasing equity in communities furthest from opportunity is more urgent than ever.

The next administration must work with Congress to quickly enact a new round of recovery or stimulus legislation. State and local governments, school systems, and small businesses continue to struggle to respond to COVID-19 and the economic and learning losses that have accompanied the resulting closures. But federal resources are not unlimited and there is little time to spare – communities need positive results quickly. It is imperative, furthermore that the administration ensures that the dollars it distributes are used effectively and equitably. The best way to do so is to use existing evidence and data — about what works, for whom. and under what circumstances — to drive recovery investments.

Fortunately, the federal government has access to unprecedented evidence and data tools that can increase the speed and effectiveness of these urgent recovery and equity-building efforts. And where evidence or data do not exist, this unique moment affords an opportunity to build evidence about what does work to help communities recover and rebuild.

Thus, one of the first priorities of the next administration’s Office of Management and Budget (OMB) should be helping agencies develop their capacity to use existing evidence and data and to build evidence where it is lacking in order to advance economic mobility across the country. OMB should also support federal agency efforts to assist state and local governments to build and use local evidence that can accelerate economic growth and help communities recover from the current crises.

Specifically, OMB should issue guidance directing federal agencies to: 1) define and prioritize evidence of effectiveness in their grant programs to help identify what works, for whom, and under what circumstances to advance economic mobility post-COVID; 2) set aside 1% of discretionary funding for evidence building, including evaluations, technical assistance and capacity building; 3) support state and local governments in using recovery funding to build their own data, evidence-building and evaluation capacity to help their communities rebuild; and 4) require that findings from 2021 evidence-building activities be incorporated into strategic plans due in 2022.