September 19, 2022 PAO-09-022-CL-03
The Strategic National Stockpile (SNS) is part of the U.S. federal medical response infrastructure, and the supplies maintained in the stockpile are intended to meet short-term public health and medical needs in the event of an emergency if immediate supply is not possible or insufficient. The SNS began as a federal bioterrorism preparedness program instituted by the Clinton administration in 1999.1 The Centers for Disease Control and Prevention were responsible for managing the “National Pharmaceutical Stockpile” of items that would be needed to respond to a biological attack. After the 9/11 terrorist attacks, Congress broadened the scope in the Bioterrorism Response Act of 2002 and the Homeland Security Act of 2002 and renamed the program the SNS.2,3
Initially, the medicines inventoried by the SNS included those that would be needed in the event of a major chemical, biological, radiological, nuclear, or explosive attack,4,5 but today the SNS has materials stockpiled to enable responses to hurricanes, earthquakes, and viral outbreaks (e.g., flu, H1N1, Ebola, Zika, COVID-19).5,6 As a result, today the SNS stockpiles more than 1,000 different types of medical supplies, including both medicines and non-pharmaceutical items, such as ventilators and personal protective equipment.7,8 In 2020, the SNS held little over $8 billion in countermeasures designed to respond to natural or manmade events, according to Greg Burel, President of Hamilton Grace, LLC and former Director of the SNS (2010–2020).
The materials are held in warehouses scattered across the United States, in close proximity to large population centers. “The objective is to get countermeasures into an area in a timeframe that is clinically relevant, whether those measures involve vaccines, materials for prophylaxis, or therapeutics to treat disease,” Burel says.
The formulary is determined by a governance body called the Public Health Emergency Medical Countermeasures Enterprise, comprising experts in disease threats and executives from various departments across the government. The group, observes Burel, works together to identify top threats and available materials that can be used either off-label or on-label to respond to those threats. It also identifies areas where new research and development should be conducted by the Biomedical Advanced Research and Development Authority (BARDA) to create new countermeasures to place into the SNS.
It is worth noting that the SNS does not just include medical supplies. Federal medical stations (FMS) are rapidly deployable caches that contain beds, supplies, and medicines used when needed to convert pre-identified buildings into temporary medical shelters. In addition, 12-Hour Push Packages each contain 50 tons of a broad spectrum of medical assets that can be delivered anywhere in the United States within 12 hours, while CHEMPACKs are containers of nerve-agent antidotes placed in secure locations at local levels to facilitate a rapid response to a chemical incident.
The COVID-19 pandemic revealed some issues with the current design and management of the SNS, including concerns about the lack of assured and appropriate funding needed to maintain a suitable level of preparedness. “Without consistent and sufficient funding, the SNS cannot place orders to acquire needed materials, and manufacturers will stop making them, particularly those that have no commercial value otherwise,” Burel explains.
Some changes may be coming, however. The U.S. House of Representatives approved The Strengthening America’s Strategic National Stockpile Act of 2021 (H.R. 3635) in October 2021.9 The Senate Health, Education, Labor, and Pensions Committee is considering its version of the bill (S. 1974), which was introduced in June 2021. Both bills call for more transparent processes for using and distributing stockpile supplies, maintaining materials in useful condition, and strengthening domestic manufacturing supply chains, among other actions.
It is also worth noting that, in March 2022, the National Institutes of Health (NIH) Countermeasures Against Chemical Threats (CounterACT) program announced intentions to open a funding solicitation to support early-stage development of new and repurposed drug candidates to mitigate the health effects resulting from exposure to chemical threats.10 Examples of chemical threat toxidromes include anticoagulants, cholinergic warfare agents, convulsants, hemolytic/metabolic disruptors, opioids, pulmonary agents, and vesicants.
No specific list of the products maintained in the SNS is provided to the public, because that information could potentially serve as a roadmap for “bad actors” to reverse-engineer attacks that could break through the country’s defenses with respect to public health, according to Burel.
The SNS includes antibiotics, antiviral drugs, vaccines, antidotes, antitoxins, medical supplies, and other pharmaceuticals. Medicines include all possible modalities, including drugs based on small molecule advanced pharmaceutical ingredients, biologics such as monoclonal antibodies, and cell therapies and vaccines based on many different technologies. The volumes maintained in the SNS are determined on a product-by-product basis, taking into account risk profiles and other factors using robust systems that model potential events, considering population data, the potential for disease spread, the mechanism of disease spread, and other factors. In some cases, these products are stored and maintained by their manufacturers and provided when needed.
Items in the SNS, including specific drugs and vaccines, are commercially available products appropriate for emergency response to specific threats. They are purchased directly for the SNS and replaced with new product when they reach their expiration dates. Older products are also obsoleted from the formulary if new products on the market provide better protection, cause fewer side effects, or otherwise offer improved performance.
When it comes to products developed specifically for the SNS, early-phase work is completed by the National Institutes of Health. Candidates that have good potential to ultimately receive U.S. FDA approval are taken up by BARDA for advanced development.
To maintain a current stock of unexpired countermeasures, procurement of commercial products is ongoing and carried out by the SNS Contracting Branch. Some are products that BARDA developed and placed into the SNS after licensure, while others were initially developed by pharmaceutical companies. Purchases are made at various times throughout the year and in various quantities, sometimes dictated by the availability of the product or the availability of funding. “The challenge is to balance the requirements in the portfolio to ensure that the SNS reduces risks to the greatest extent possible across all possible threats,” Burel comments.
The Committee has a 10-year horizon with respect to advances in technology to ensure that optimum solutions are in place to respond to various threats. In addition to advances in medical technology, logistics considerations are also important, particularly, Burel notes, given the increasing portion of drugs and vaccines that require cold-chain storage.
When possible, the SNS seeks to source products from U.S.-based suppliers, for reasons ranging from national security concerns to basic logistics. “The difficulty of shipping and handling large quantities of these products in a rapid manner impacts the quantities purchased for the stockpile, as well as where they will be sited, how they will be stored long-term, and what needs to be done to ensure that state and local partners can receive and use them at the time of need — in essence, the nature of the required response plans,” explains Burel.
When the SNS procures medical products on the open market, quotes for manufacturing are generally sought that will afford the best terms and conditions at the quantities required and with timing that allows for appropriate cycling of expired materials. For the products developed by BARDA, that agency establishes contracts for the manufacture of new drugs intended for stockpiling.
The COVID-19 pandemic, Burel notes, brought the fragility of the pharmaceutical supply chain to the attention of the SNS management. As a result, domestic manufacturers are increasingly sought that have end-to-end capabilities from raw material to fill/finish so as to avoid potential supply interruptions due to geopolitical issues, such as another global pandemic. The SNS also seeks to achieve redundancy of supply to increase supply chain security. Redundant suppliers are not always available, however, observes Burel, because often there is no commercial market for the medications inventoried by the SNS; their only purpose is as countermeasures to specific threats, and therefore there is often only a single supplier.
The SNS procurement process considers particular needs around particular products, according to Burel. Products must be approved by the FDA and manufactured in FDA-audited facilities, within the United States whenever possible. Suppliers must have experience and the demonstrated capability to deliver products in the quantities needed and timeframes required. They must have track records of good compliance with Current Good Manufacturing Practices. In some cases, when it is necessary to ensure that a manufacturer can provide the product with the exact quality and other attributes that we require when we need it, such as those with highly complex structures that lead to purification challenges, a site visit will be made.
For contract manufacturers, the key to the successful supply of drug products, whether to the government for the SNS or pharmaceutical customers, is the establishment of a trusting relationship. Building that trust is absolutely essential and ties back to the ability of the contract manufacturer to demonstrate that it has the ability to perform at a high level so that expectations with respect to safety, quality, and delivery of product on time and in full can be met or exceeded. Suppliers involved in biodefense projects must also understand the SNS and its demand cycle and have the infrastructure necessary to produce products securely.
Supplying the biodefense market, and the SNS particularly, means manufacturing products for the government to inventory against a potential future need. It is quite different from supplying an API or drug product to a pharmaceutical company for which there is ongoing and potentially increasing demand. Rather than continuous supply, manufacturing is much more cyclical, with production of batches taking place much less frequently and driven by the expiration date of the product.
Scorpion Biological Services is a member of the NightHawk Biosciences ecosystem, which comprises five discrete companies involved in drug development and manufacturing. Skunkworx Bio focuses on early R&D of novel modalities, while Heat Biologics specializes in immunomodulatory therapies. Elusys Therapeutics provides drugs that support counterterrorism efforts, and Pelican Therapeutics develops next-generation cell therapies. Scorpion provides development and manufacturing services to external customers, as well as NightHawk subsidiaries.
Elusys established the initial relationship with the government’s biodefense program. The company developed the anthrax antitoxin ANTHIM® (obiltoxaximab) for the treatment and prevention of inhalational anthrax caused by Bacillus anthracis in children and adults under a BARDA contract with the SNS. The product is still stockpiled, and more of the product has been ordered in preparation for the current material in the SNS approaching its expiry date.
Greg Burel is joined by other experienced biodefense experts on the NightHawk Advisory Board on Biodefense, which provides advice on a range of issues, including possible drug products that might be needed for the SNS in the future and how modern technologies might be applied to improve the production and performance of current SNS materials.
As part of NightHawk, Scorpion Biological Services is being configured to support both clinical and commercial manufacturing of drug substances and drug products, including the production of ANTHIM® for the Elusys biodefense program. Previously, Elusys outsourced the manufacturing of ANTHIM®.
Construction of a new commercial pharmaceutical manufacturing facility in Manhattan, Kansas, with the appropriate infrastructure for the production of biodefense products is allowing the move to in-house manufacture of ANTHIM®. The Manhattan region features a concentration of biodefense organizations, including Kansas State University’s Biosecurity Research Institute (BRI) and the National Bio and Agro-Defense Facility (NBAF) — the U.S. government’s agricultural biothreat research laboratory — as well as the U.S. Army base at Fort Riley, which facilitates military delivery of drug products to the SNS. This new facility complements our existing clinical manufacturing site located in San Antonio, Texas.
Although Scorpion’s involvement in the production of biodefense projects is fortuitous and made possible through its position as a member of the NightHawk ecosystem, the company has all of the attributes desirable in a contract manufacturing supplier to the SNS.
First, Scorpion’s scientific team has extensive experience developing and manufacturing a diverse array of drug substances and drug products, including cell therapies; recombinant proteins, cytokines, and monoclonal antibodies (mAbs) produced via cell culture; proteins, peptides, and other molecules manufactured via microbial fermentation; and many others.
Second, the San Antonio facility is well-equipped to handle not only different modalities but also different modalities simultaneously without concern for cross-contamination. The main facility is set up in a pod-type format, with each cleanroom operating on separate air handlers, and all equipment, personnel, and product flows are unidirectional. In addition, disposable technologies and closed systems are employed throughout the facility. A separate building on the campus is dedicated to microbial fermentation.
Third, we have both development and manufacturing capabilities, as well as expertise in engineering and scaling. Processes are developed with the needs for commercial production in mind from the outset, ensuring the development of robust and scalable solutions. In addition, the equipment that will be installed in the commercial-scale facility are of the same configuration as the equipment used at the clinical site to facilitate scale-up, and the largest development equipment used at the San Antonio site will also be installed at the Manhattan facility to streamline the tech transfer of projects from one site to the other.
Fourth, in addition to development and manufacturing expertise in San Antonio, Scorpion also has extensive analytical, quality, and regulatory capabilities to support all aspects of biologic projects (e.g., cell therapies, mAbs, recombinant proteins) as they progress from early to later development stages. For unique characterization requirements, we have an extensive network of partner CROs with specialized expertise. As a full-service contractor with all major capabilities in-house and years of experience working with a wide variety of biologic candidates, we are able to reduce project timelines and costs.
Finally, being a part of the NightHawk ecosystem is quite advantageous with respect to Scorpion’s ability to support biodefense projects. The anthrax antitoxin is just one product that could be of interest to the SNS. “We need to continue to look at new countermeasures to address emergent needs. In addition to ANTHIM® as one of a couple of available countermeasures for anthrax, the RapidVax® vaccine platform being developed by Elusys shows promise as a new approach to countering emerging biological threats. As a result, “there is a good fit for Scorpion Bio and the other NightHawk subsidiaries in the biodefense space,” observes Burel.
The successful support of biodefense projects and the associated relationship with the government that such projects require will be beneficial for Scorpion. Trust with customers is built on experience and success. The more successful we are with biodefense projects, the more attractive we will be to non-government-related entities, particularly small pharma and biotech firms that lack the resources to pursue in-house development and manufacturing. Producing products for the SNS at commercial scale will increase Scorpion Biological Services’ credibility.
The benefits of being part of an ecosystem such as that established by NightHawk are profound. We have the opportunity to collaborate with companies involved in a wide array of novel technologies to develop fascinating new therapies. We can leverage the expertise that they have amassed in their particular focus areas to improve and expand the capabilities of Scorpion.
In turn, Scorpion is able to support and facilitate the activities at the other companies within the NightHawk ecosystem. For instance, as a near-virtual company, Skunkworx has outsourced the manufacturing and testing of its novel candidates but will soon be leveraging Scorpion as an “in-house” service.
It is important to stress, however, that every single company within the NightHawk ecosystem remains independently operated. No computer-related infrastructure is shared between the different organizations. Scorpion signs formal development and manufacturing service agreements with the other NightHawk companies before any projects are initiated. As such, there are no conflict-of-interest concerns, regardless of what targets and candidates external customers bring to Scorpion Bio.
As a U.S.-based CDMO with wide expertise in the development and manufacturing of a broad range of modalities and a demonstrated track record of compliance, safety, quality, and on-time in-full delivery, Scorpion Biological Services is well positioned to be a strong partner for U.S. biodefence efforts and the SNS. This position is further strengthened by Scorpion’s analytic and regulatory capabilities and expertise in engineering and scaling and our association with Elusys and the rest of the NightHawk ecosystem, as well as our deep understanding of the SNS and its demand cycle, which is supported by the biodefense experts on NightHawk’s advisory board. The construction of a new commercial-scale manufacturing facility in the biodefense hub of Manhattan, Kansas, will allow Scorpion to expand its ability to support biodefense programs into the future.
Brian is responsible for the cGMP manufacturing-related activities of biologics, including technology transfer, process characterization, facility fit, and manufacture of clinical-grade biologics. Brian has more than 20 years of industrial biotechnology experience in downstream process development of early- and late-stage protein therapeutics from mammalian and microbial expression systems.