Promoting medical innovation is a clear priority for U.S. government agencies focused on healthcare. President Trump’s series of healthcare executive orders and the Department of Health and Human Services’ recent Operation TrialBlazer highlight the necessity of using innovation to deliver the best outcomes for patients.[1] While policymakers and the public tend to focus on discovery of new drugs and treatments, the role of advances in drug delivery mechanisms tends to be overlooked. Innovations in drug delivery can improve adoption of lifesaving treatments, expand the number of people capable of administering care, and improve patient outcomes in time-sensitive emergencies. Delivery format is not a cosmetic detail; it is often the decisive variable determining whether a proven treatment reaches a patient in time.
Drug delivery systems remain a critical component of medical research, development, and deployment. Modern drug delivery technology can be traced to the 1950s, when the first delayed-release drug capsule was introduced into the commercial market.[2] The purpose of this briefing note is to briefly explore the value of drug delivery system innovation in emergency situations.
In many emergencies, the clinical value of a medicine depends not only on whether it works, but on whether it can be delivered quickly, correctly, and confidently outside a hospital setting. A treatment with strong clinical evidence can still fail to save lives if its administration requires intravenous (IV) access, extensive training, or specialized personnel that are unavailable in the critical first minutes of an emergency. The same principles apply whether responding to an opioid overdose, a mass-casualty event, or a battlefield injury.
In the arena of emergency response, delivery formats such as nasal sprays, prefilled syringes, and autoinjectors are particularly effective in improving patient outcomes. Easy-to-use delivery formats can reduce training burdens, shorten time to treatment, and extend administration of lifesaving interventions beyond trained specialists. Delivery format of drugs is therefore a core element of effective preparedness.
Case studies from opioid overdose and trauma care demonstrate that innovations in medicine delivery can be as transformative as the medicines themselves. In both cases, the underlying therapies were already proven safe and effective through years of clinical use. Yet their public health impact remained constrained by delivery methods that required trained medical professionals, specialized equipment, or formal healthcare facilities. By redesigning how these medicines are administered – making them simpler, faster, and accessible to non-specialists – delivery innovations have expanded the population capable of providing lifesaving treatment, shortened the time to intervention, and improved patient outcomes. The following examples illustrate how advances in drug delivery can unlock the full potential of established therapies and provide a model for future investments in medical countermeasures and emergency preparedness. They also underscore the importance of ensuring that such products are adopted broadly across all pre-hospital organizations delivering emergency care, so that life-saving treatments are available at the point of injury regardless of which responder reaches the patient first.
Naloxone has long been the standard treatment for opioid overdose, but for many years the innovator Narcan was only available as a parenteral injection, to be administered IV, subcutaneously or intramuscularly. Since the most rapid onset of action is achieved by the IV route, this was the route recommended in emergency situations such as opioid overdose. As such, administration of naloxone for opioid overdose was mostly limited to trained healthcare professionals. Injectable naloxone required specialized knowledge and experience, largely limiting its use to physicians, nurses and paramedics.
In November 2015, the FDA approved a new route of administration for Narcan, authorizing a 4 mg nasal spray formulation.[3] The approval marked the first step in widening the pool of people that could administer naloxone. First responders routinely began administering naloxone via nasal spray, but the product remained prescription-only, limiting its use by the general public The second development that significantly expanded access to intranasal naloxone occurred in March 2023, when the FDA changed the regulatory status of intranasal Narcan and approved it for over-the-counter (OTC), nonprescription use. This was the first naloxone product ever approved without a prescription.[4] The agency’s own rationale centered on delivery and usability: the manufacturer demonstrated that ordinary consumers could understand how to administer the drug safely and effectively without supervision from a healthcare professional. The OTC status opened intranasal naloxone to sale in drugstores, convenience stores, grocery stores, and online retailers, without changing the underlying molecule. Only the packaging and labeling changed. A second OTC nasal-spray product, RiVive, followed in July 2023, further widening consumer access. [5]
The nasal-spray delivery, followed by a regulatory Rx-to-OTC switch, was central to making intranasal Narcan usable by non-medical bystanders in real-world emergencies. The lesson for policymakers is straightforward: the same medicine reached a far larger population of potential rescuers only after its delivery format was redesigned for general public use.
Real-world example: A commuter becomes the first responder
In March 2023, while waiting for a subway train, a commuter noticed an unconscious man with slow, shallow breathing and suspected an opioid overdose.[6] Carrying Narcan nasal spray in her backpack, she administered a single intranasal dose while another bystander called 911. Within minutes, the man regained consciousness before EMS arrived. Afterwards, she remarked that administering the medication was “anticlimactic” because it was so simple. No assembly nor dose calculation was required.
This case illustrates how a prefilled, single-use nasal spray can be administered by virtually anyone with minimal training. The innovation was not a new drug, but a new delivery platform that transformed millions of ordinary citizens into potential first responders. Real-world experience has validated this approach. Early community use of Narcan nasal spray demonstrated successful overdose reversals in nearly 99% of documented cases, with most patients responding within five minutes.[7]
Policy lesson: The widespread impact of naloxone was achieved not by discovering a better antidote, but by redesigning how the antidote reaches the patient.
Tranexamic acid (TXA) helps stabilize blood clots and reduce blood loss in severe bleeding emergencies. Its clinical value is well established and continues to be reinforced by new evidence. The latest evidence comes from the Canadian TRACTION trial. The results found that a hospital-wide policy of administering TXA to patients undergoing major noncardiac surgery reduced the proportion of patients needing red-cell transfusion from 9.8% to 7.4%, without increasing the 90-day rate of venous thromboembolism, which held steady at 2.1% in both the treatment and placebo groups.[8]
That trial, which followed more than 8,000 major surgeries across ten Canadian hospitals, reinforces TXA’s safety and effectiveness even in higher-risk populations such as cancer patients, who made up roughly 60% of the study cohort. However, the trial also highlights a structural limitation for the use of TXA. In a hospital setting, TXA can be delivered through routine IV with trained clinicians. That same infrastructure does not exist in the field.
In prehospital trauma settings, IV access can be difficult to establish and delays can be fatal, particularly in mass-casualty, combat, or remote scenarios. To close the treatment gap, a new TXA delivery approach is being developed with the backing of the Biomedical Advanced Research and Development Authority (BARDA). In November 2025, BARDA awarded Rafa Laboratories a contract worth up to $186 million to develop an intramuscular formulation of TXA for prehospital care, with development of a TXA autoinjector included in the project scope.[9] Instead of relying solely on IV delivery of TXA, the U.S. government is investing in a new delivery solution that is better suited to the realities of emergency or battlefield scenarios.
TXA has become a standard component of modern trauma care. Combat trauma, in particular, provides one of the clearest demonstrations of both TXA’s value and its delivery realities.[10]
In the U.S., the Committee on Tactical Combat Casualty Care (CoTCCC) operates under the Joint Trauma System (JTS), which is part of the U.S. Defense Health Agency (DHA). According to the 2026 TCCC guidelines, TXA should be administered to military casualties if the casualty will likely need a blood transfusion (for example: presents with hemorrhagic shock, one or more major amputations, penetrating torso trauma, or evidence of severe bleeding).[11]
In one documented case, a service member sustained multiple gunshot wounds and arrived in critical condition, with a serious abdominal injury and severely compromised breathing. Combat medics worked rapidly to control bleeding and stabilize him, but were unable to establish IV access under the chaos of battlefield conditions. Rather than delay treatment, the medic administered TXA intramuscularly (IM) – an off-label route, but a decision that proved to be life-saving for the patient.[12]
This case highlights the challenge of administering an IV drug in the heat of combat. Highly trained military medics must establish IV access, prepare the medication, and administer it under extraordinarily stressful conditions. These steps consume valuable time and require advanced medical skills that may not be available during combat scenarios. IV administration may also be challenging in mass-casualty incidents, in rural settings, or among civilian first responders. Time is precious in the moments following a traumatic injury. In one example, reducing time-to-treatment in a trauma scenario from the traditional 3-hour window to within 90 minutes was associated with a meaningfully lower 28-day mortality rate in an exploratory analysis of the PATCH-Trauma trial cohort, reinforcing that speed of administration may be the critical variable.[13]
Since traumatic hemorrhage often occurs outside of the hospital setting, appreciation for the potential utility of administering TXA in the prehospital space is growing. For example, experience from the Israel Defense Forces demonstrated that administering TXA in the prehospital environment allowed treatment significantly closer to the time of injury, without delaying evacuation or producing safety concerns.[14] In 2015, the NATO Blood Panel issued recommendations for the use of TXA for the management of uncontrolled bleeding, including in the prehospital setting by trained medics.[15]
Widespread adoption of prehospital administration of TXA for traumatic hemorrhage requires a delivery mode other than the IV route, due to the limitations cited above. An intramuscular autoinjector would address precisely this operational gap. Rather than requiring IV equipment, medication preparation, and advanced training, responders could administer a fixed intramuscular dose within seconds. While a TXA autoinjector remains under development and is not yet available commercially, the approach follows the same logic that transformed access to epinephrine autoinjectors and naloxone nasal spray. The underlying medicine remains unchanged; what changes is the ease of use and the number of people capable of delivering it during the critical first minutes after injury.
Policy lesson: TXA has already proven its clinical value. The next frontier is ensuring that treatment can be delivered efficiently at the point of injury, rather than only after IV access is established by trained personnel.
The case studies for naloxone and TXA presented here illustrate the same policy principle. In both cases, the pharmacology was already well established. The transformative innovation lies in delivery technology that moves treatment from hospitals to the point of need, expands the pool of capable responders, and compresses the time between injury and intervention. For policymakers seeking to improve preparedness, investment in medicine delivery systems can be just as consequential as investment in new medicines themselves. Policymakers should also ensure that such technologies are adopted broadly across all pre-hospital organizations to maximize timely access to life-saving treatment before hospital arrival. This includes military medical services, EMS, fire and rescue services, law enforcement agencies, search and rescue teams, and other first-response organizations. As governments continue investing in preparedness, emergency response, and medical countermeasures, these examples raise broader questions about the role of drug delivery innovation.
A medicine that is difficult to administer in the moment when it is most needed may fail to reach its full public health value. As the naloxone and TXA examples show, delivery innovation can turn an already-effective treatment into a usable, scalable, lifesaving tool – extending its reach from specialists in a hospital to first responders and bystanders in the field. Preparedness policy should reward that shift. Active drugs and their delivery modes should be evaluated as one comprehensive, integrated product – with each aspect contributing to the full potential of the product to enhance public health.
Note to Reader: Rafa Biodefense is currently developing the intramuscular (IM) formulation of tranexamic acid (TXA) in collaboration with BARDA. TXA autoinjectors are not yet currently available.
[2] Park H, Otte A, Park K. “Evolution of drug delivery systems: From 1950 to 2020 and beyond.” Journal of Controlled Release. 2022;342:53-65. doi:10.1016/j.jconrel.2021.12.030. Available at: https://www.sciencedirect.com/science/article/pii/S0168365921006830
[3] U.S. Food and Drug Administration. “FDA moves quickly to approve easy-to-use nasal spray to treat opioid overdose.” FDA News Release, Nov 18, 2015. https://wayback.archive-it.org/7993/20170112022854/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm473505.htm
[4] U.S. Food and Drug Administration. “FDA Approves First Over-the-Counter Naloxone Nasal Spray.” FDA Press Announcement, March 29, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-over-counter-naloxone-nasal-spray
[5] U.S. Food and Drug Administration. “FDA Approves Second Over-the-Counter Naloxone Nasal Spray Product.” FDA Press Announcement, July 28, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-second-over-counter-naloxone-nasal-spray-product
[6] The Washington Post. “These people used Narcan to save a life. Here’s how they did it.” December 2024.
https://www.washingtonpost.com/wellness/interactive/2024/narcan-naloxone-overdose-opioid/
[7] Avetian GK, Fiuty P, Mazzella S, Koppa D, Heye V, Hebbar P. Use of naloxone nasal spray 4 mg in the community setting: a survey of use by community organizations. Curr Med Res Opin. 2018 Apr;34(4):573-576. doi: 10.1080/03007995.2017.1334637. Epub 2017 Jun 7. PMID: 28535115. Available at https://pubmed.ncbi.nlm.nih.gov/28535115/
[8] Houston, B.L., McIsaac, D.I., et al. “Hospital Policy of Tranexamic Acid to Reduce Transfusion in Major Noncardiac Surgery” (The TRACTION Trial). N Engl J Med. 2026 Jun 25;394(24):2419-2428. Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa2515820
[9] Rafa Laboratories. “Rafa Laboratories Awarded up to $186 Million by BARDA to Develop a Life-Saving Intramuscular TXA Injection for Prehospital Care.” PR Newswire, November 19, 2025. https://www.prnewswire.com/news-releases/rafa-laboratories-awarded-up-to-186-million-by-barda-to-develop-a-life-saving-intramuscular-txa-injection-for-prehospital-care-302618865.html
[10] Morrison JJ, Dubose JJ, Rasmussen TE, Midwinter MJ. Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. Arch Surg. 2012 Feb;147(2):113-119.
[11] Committee on Tactical Combat Casualty Care (CoTCCC). Tactical Combat Casualty Care (TCCC) Guidelines. Joint Trauma System (JTS), Defense Health Agency; effective 1 May 2026.
[12] Steele D, Ballard PK, Burke R, Ferguson B. Intramuscular Tranexamic Acid Administration on the Battlefield.
Case Rep Emerg Med. 2022 Oct 13;2022:9689923. Available at: https://pubmed.ncbi.nlm.nih.gov/36277170/
[13] Ali A, Gruen RL, Bernard SA, et al. Tranexamic Acid Timing and Mortality Impact After Trauma. Ann Emerg Med. 2026 Jan;87(1):83-89.
[14] Lipsky AM, Abramovich A, Nadler R, et al. “Prehospital Administration of Tranexamic Acid in Trauma Patients: The Israel Defense Forces Experience.” Injury. 2014;45(1):66-70. Available at: https://www.sciencedirect.com/science/article/pii/S0020138313003847
[15] Heier HE, et al. Use of Tranexamic Acid in Bleeding Combat Casualties. Mil Med 2015 Aug;180(8):844-846.
