The Emergency Use Authorization of Pharmaceuticals: History and Utility During the COVID-19 Pandemic.

The Emergency Use Authorization (EUA) originated in 2004 because of the need for emergency medical countermeasures (MCMs) against potential bioterrorist attacks. The EUA also proved useful in dealing with subsequent pandemics and has emerged as a critical regulatory pathway for therapeutics and vaccines throughout the Coronavirus Disease 2019 (COVID-19) pandemic. With the EUA process in the USA, we witnessed emergency authorizations, their expansions, as well as withdrawal of previously authorized products, which exemplifies the dynamic nature of scientific review of EUA products. EUAs proved vital for the first group of COVID-19 vaccines, including the temporary pause of one vaccine while emergency safety issues were evaluated. Although this review on the EUA is primarily focused on the USA, distinctions were made with other jurisdictions such as Europe and Canada with respect to the emergency authorizations of the vaccines. Finally, we discuss some important differences following EUA and formal new drug/vaccine application (NDA/BLA) approvals.

Biowarfare, bioterrorism and biocrime: A historical overview on microbial harmful applications.

Microbial Forensics is a field that continues to grow in interest and application among the forensic community. This review, divided into two sections, covers several topics associated with this new field. The first section presents a historic overview concerning the use of microorganisms (or its product, i.e. toxins) as harmful biological agents in the context of biological warfare (biowarfare), bioterrorism, and biocrime. Each case is illustrated with the examination of case reports that span from prehistory to the present day. The second part of the manuscript is devoted to the role of MF and highlights the necessity to prepare for the pressing threat of the harmful use of biological agents as weapons. Preventative actions, developments within the field to ensure a timely and effective response and are discussed herein.

Links between law enforcement and veterinary animal health: a case study of the United Kingdom and the United States of America.

The anthrax attacks carried out in the United States of America in the latter part of 2001 served as a clarion call to most law enforcement agencies among developed countries as, until this time, they had not recognised the threat posed by the criminal use of pathogens and/or toxins. Law enforcement agencies include the local and federal police, Customs, Immigration and any other agencies that perform a law-enforcing role. That a criminal or terrorist group could commit such an act was considered nearly inconceivable, even though biological weapons had been used against humans and animals in warfare many times over the last several hundred years. Similarly, it is without doubt that the terrorist threat to all societies changed after the events of 11 September 2001 during which the clear intention had been to cause as many fatalities and casualties as possible. As a result, the biological threat to human health became a focus for many governments.

Les attaques à la fièvre charbonneuse perpétrés aux États-Unis d'Amérique à la fin de l'année 2001 ont lancé un signal d'alerte à la plupart des agences chargées de l'application des lois des pays développés, qui n'avaient jusqu'alors pas pris conscience des menaces posées par l'utilisation criminelle des agents pathogènes et/ou des toxines. Les agences chargées de l'application des lois sont notamment les forces de police locales et fédérales, les services des douanes, les services d'immigration et toute autre agence gouvernementale chargée du maintien de l'ordre et de la justice. Il était pratiquement inconcevable qu'un groupe criminel ou terroriste puisse commettre un tel acte, même si des armes biologiques avaient déjà été utilisées contre les populations humaines et animales au cours de certains conflits armés des siècles précédents. De même, il va sans dire que la menace terroriste pesant sur les sociétés dans leur ensemble a pris un nouveau visage après les événements du 11 septembre 2001, dont le but était clairement de faire le plus de victimes possible et de tuer le plus grand nombre de personnes possible. En conséquence, la menace biologique pesant sur la santé publique est devenue un domaine central d'attention pour nombre de gouvernements.

Los ataques con la bacteria del carbunco perpetrados en los Estados Unidos de América a finales de 2001 marcaron un antes y un después para la mayoría de los cuerpos de seguridad de los países desarrollados, que hasta la fecha no habían advertido la amenaza que planteaba el uso de patógenos y/o toxinas con fines criminales. Forman parte de los cuerpos de seguridad las fuerzas de policía local y federal, los cuerpos de aduanas, inmigración y demás instituciones cuya función consiste en velar por el cumplimiento de la ley. Que un grupo delictivo o terrorista pudiera cometer semejante acto era algo prácticamente inconcebible, aun cuando en los últimos siglos hayan menudeado los ejemplos de utilización de armas biológicas contra la población humana o animal como instrumento de guerra. Análogamente, no cabe duda alguna de que la amenaza terrorista que planea sobre todas las sociedades cambió a partir de los acontecimientos del 11 de septiembre de 2001, en los que la intención era claramente de causar tantos muertos y heridos como fuera posible. A resultas de aquello, las amenazas biológicas para la salud humana pasaron a ser una de las preocupaciones cardinales de muchos gobiernos.

Military Importance of Natural Toxins and Their Analogs.

Toxin weapon research, development, production and the ban on its uses is an integral part of international law, with particular attention paid to the protection against these weapons. In spite of this, hazards associated with toxins cannot be completely excluded. Some of these hazards are also pointed out in the present review. The article deals with the characteristics and properties of natural toxins and synthetic analogs potentially constituting the basis of toxin weapons. It briefly describes the history of military research and the use of toxins from distant history up to the present age. With respect to effective disarmament conventions, it mentions certain contemporary concepts of possible toxin applications for military purposes and the protection of public order (suppression of riots); it also briefly refers to the question of terrorism. In addition, it deals with certain traditional as well as modern technologies of the research, synthesis, and use of toxins, which can affect the continuing development of toxin weapons. These are, for example, cases of new toxins from natural sources, their chemical synthesis, production of synthetic analogs, the possibility of using methods of genetic engineering and modern biotechnologies or the possible applications of nanotechnology and certain pharmaceutical methods for the effective transfer of toxins into the organism. The authors evaluate the military importance of toxins based on their comparison with traditional chemical warfare agents. They appeal to the ethics of the scientific work as a principal condition for the prevention of toxin abuse in wars, military conflicts, as well as in non-military attacks.

Contextual Factors Among Indiscriminate or Large Attacks on Food or Water Supplies, 1946-2015.

This research updates previous inventories of malicious attacks on food and water and includes data from 1946 through mid-2015. A systematic search of news reports, databases, and previous inventories of poisoning events was undertaken. Incidents that threatened or were intended to achieve direct harm to humans and that were either relatively large (more than 4 victims) or indiscriminate in intent or realization were included. Agents could be chemical, biological, or radionuclear. Reports of candidate incidents were subjected to systematic inclusion and exclusion criteria as well as validity analysis (not always clearly undertaken in previous inventories of such attacks). We summarize contextual aspects of the attacks that may be important for scenario prioritization, modelling, and defensive preparedness. Opportunity, and particularly access to dangerous agents, is key to most realized attacks. The most common motives and relative success rate in causing harm were very different between food and water attacks. The likelihood that people were made ill or died also varied by food or water mode and according to motive and opportunity for delivery of the hazardous agent. Deaths and illness associated with attacks during food manufacture and prior to sale have been fewer than those in some other contexts. Valuable opportunities for food defense improvements are identified in other contexts, especially food prepared in private or community settings.

John Bartlett and bioterrorism.

Until 1997, the subject of bioterrorism was not discussed within the medical community and deliberately ignored in national planning efforts. Biological weapons were regarded as "morally repulsive." This complacency stemmed from a 1972 Biological Weapons Convention where all countries agreed to cease offensive biological weapons research. In the 1990s, however, the Soviet Union was discovered to have an extensive bioweapons program and a Japanese religious cult sought to launch an anthrax attack on Tokyo. Biological weapons such as smallpox and anthrax had the potential to cause a national catastrophe. However, little was done until John Bartlett in 1997 led a symposium and program to educate the medical community and the country of the need for definitive bioweapons programs. It was highly persuasive and received a final stimulus when the anthrax attack occurred in the United States in 2001.

History of biological warfare and bioterrorism.

Bioterrorism literally means using microorganisms or infected samples to cause terror and panic in populations. Bioterrorism had already started 14 centuries before Christ, when the Hittites sent infected rams to their enemies. However, apart from some rare well-documented events, it is often very difficult for historians and microbiologists to differentiate natural epidemics from alleged biological attacks, because: (i) little information is available for times before the advent of modern microbiology; (ii) truth may be manipulated for political reasons, especially for a hot topic such as a biological attack; and (iii) the passage of time may also have distorted the reality of the past. Nevertheless, we have tried to provide to clinical microbiologists an overview of some likely biological warfare that occurred before the 18th century and that included the intentional spread of epidemic diseases such as tularaemia, plague, malaria, smallpox, yellow fever, and leprosy. We also summarize the main events that occurred during the modern microbiology era, from World War I to the recent 'anthrax letters' that followed the World Trade Center attack of September 2001. Again, the political polemic surrounding the use of infectious agents as a weapon may distort the truth. This is nicely exemplified by the Sverdlovsk accident, which was initially attributed by the authorities to a natural foodborne outbreak, and was officially recognized as having a military cause only 13 years later.

The plague of Athens: an ancient act of bioterrorism?

Recent data implicate Salmonella enterica serovar Typhi as a causative pathogen of the Plague of Athens during the Peloponnesian War (430-426 bc). According to Thucydides, the sudden outbreak of the disease may link to poisoning of the water reservoirs by the Spartans. The siege of a city was aimed at exhausting the supplies of a population, which often led to the outbreak and spread of epidemics. Poisoning of the water reservoirs of a besieged city as an act of bioterrorism would probably shorten the necessary time for such conditions to appear.

Historical perspective on agroterrorism: lessons learned from 1945 to 2012.

This article presents a historical perspective on agroterrorism cases from 1945 until 2012. The threat groups and perpetrators associated with bio- and agroterrorism are clustered into several groups: apocalyptic sects, lone wolves, political groups, and religious groups. We used open-source information, and 4 biological agroterrorism cases are described: (1) in 1952, Mau Mau poisoned cattle in Kenya by using a plant toxin from the African milk bush plant; (2) in 1985, the USDA claimed that Mexican contract workers were involved in deliberately spreading screwworm (Cochliomyia hominivorax) among livestock; (3) in 2000, Palestinian media reported that Israeli settlers released sewer water into Palestinian agricultural fields; and (4) in 2011, a person was sentenced to prison after threatening US and UK livestock with the deliberate spread of foot-and-mouth disease virus. All 4 cases can be assigned to political groups. These cases have not attracted much attention in literature nor in the public media, and the credibility of the sources of information varies. We concluded that agroterrorism has not been a problem during the period studied. Lessons learned from the few cases have generated awareness about the fact that nontypical biological weapons and non-high-risk agents, such as African milk bush, screwworm, and sewer water, have been used by attackers to influence local decision makers. This review will be useful in improving future preparedness planning and developing countermeasures.

Disinformation squared: was the HIV-from-Fort-Detrick myth a Stasi success?

BACKGROUND: When in May 1983 the acquired immunodeficiency syndrome (AIDS) was first securely attributed to a virus, eventually called the human immunodeficiency virus (HIV), many controversies arose. Among these was one centering on HIV's origin. A startling hypothesis, called here the "HIV-from-Fort-Detrick myth," asserted that HIV had been a product, accidental or intentional, of bioweaponry research. While its earliest identifiable contributors were in the West, this myth's most dynamic propagators were in the East. The Soviet security service, the KGB, took "active measures" to create and disseminate AIDS disinformation beginning no later than July 1983 and ending no earlier than October 1987. The East German security service, a complex bureaucracy popularly known as "the Stasi," was involved, too, but how early, how deeply, how uniformly, how ably, and how successfully has not been clear. Following German reunification, claims arose attributing to the Stasi the masterful execution of ingenious elements in a disinformation campaign they helped shape and soon came to dominate. We have tested these claims. QUESTION: Was the HIV-from-Fort-Detrick myth a Stasi success? METHODS: Primary sources were documents and photographs assembled by the Ministry of State Security (MfS) of the German Democratic Republic (GDR or East Germany), the Ministry of Interior of the People's Republic of Bulgaria, and the United States Department of State; the estate of myth principals Jakob and Lilli Segal; the "AIDS box" in the estate of East German literary figure Stefan Heym; participant-observer recollections, interviews, and correspondence; and expert interviews. We examined secondary sources in light of primary sources. FINDINGS: The HIV-from-Fort-Detrick myth had debuted in print in India in 1983 and had been described in publications worldwide prior to 1986, the earliest year for which we found any Stasi document mentioning the myth in any context. Many of the myth's exponents were seemingly independent conspiracy theorists. Its single most creative exponent was Jakob Segal, an idiosyncratic Soviet biologist long resident in, and long retired in, the GDR. Segal applied to the myth a thin but tenacious layer of plausibility. We could not exclude a direct KGB influence on him but found no evidence demonstrating it. The Stasi did not direct his efforts and had difficulty tracking his activities. The Stasi were prone to interpretive error and self-aggrandizement. They credited themselves with successes they did not achieve, and, in one instance, failed to appreciate that a major presumptive success had actually been a fiasco. Senior Stasi officers came to see the myth's propagation as an embarrassment threatening broader interests, especially the GDR's interest in being accepted as a scientifically sophisticated state. In 1986, 1988, and 1989, officers of HV A/X, the Stasi's disinformation and "active measures" department, discussed the myth in meetings with the Bulgarian secret service. In the last of these meetings, HV A/X officers tried to interest their Bulgarian counterparts in taking up, or taking over, the myth's propagation. Further efforts, if any, were obscured by collapse of the East German and Bulgarian governments. CONCLUSION: No, the HIV-from-Fort-Detrick myth was not a Stasi success. Impressions to the contrary can be attributed to reliance on presumptions, boasts, and inventions. Presumptions conceding to the Stasi an extraordinary operational efficiency and an irresistible competence - qualities we could not confirm in this case - made the boasts and inventions more convincing than their evidentiary basis, had it been known, would have allowed. The result was disinformation about disinformation, a product we call "disinformation squared."

From biodefence to biosecurity: the Obama administration's strategy for countering biological threats.

The Seventh Review Conference of the Biological Weapons Convention (BWC), the first international treaty to outlaw an entire class of weapons, was held in Geneva in December 2011. On 7 December, Secretary of State Hillary Clinton became the highest-ranking US government official to address a BWC meeting. Secretary Clinton told the assembled delegation that 'we view the risk of bioweapons attack as both a serious national security challenge and a foreign policy priority'. At the same time, she warned that a large-scale disease outbreak 'could cripple an already fragile global economy'. Secretary Clinton's speech reflected a new understanding that the range of biological threats to international security has expanded from state-sponsored biological warfare programmes to include biological terrorism, dual-use research and naturally occurring infectious diseases such as pandemics. Recognizing these changes, President Barack Obama released a new national strategy for countering biological threats in 2009. This strategy represents a shift in thinking away from the George W. Bush administration's focus on biodefence, which emphasized preparing for and responding to biological weapon attacks, to the concept of biosecurity, which includes measures to prevent, prepare for and respond to naturally occurring and man-made biological threats. The Obama administration's biosecurity strategy seeks to reduce the global risk of naturally occurring and deliberate disease outbreaks through prevention, international cooperation, and maximizing synergies between health and security. The biosecurity strategy is closely aligned with the Obama administration's broader approach to foreign policy, which emphasizes the pragmatic use of smart power, multilateralism and engagement to further the national interest. This article describes the Obama administration's biosecurity strategy; highlights elements of continuity and change from the policies of the Bush administration; discusses how it fits into Obama's broader foreign policy agenda; and analyses critical issues that will have to be addressed in order to implement the strategy successfully.

Insects as weapons of war, terror, and torture.

For thousands of years insects have been incorporated into human conflict, with the goals of inflicting pain, destroying food, and transmitting pathogens. Early methods used insects as "found" weapons, functioning as tactical arms (e.g., hurled nests) or in strategic habitats (e.g., mosquito-infested swamps). In the twentieth century the relationship between insects and disease was exploited; vectors were mass-produced to efficiently deliver pathogens to an enemy. The two most sophisticated programs were those of the Japanese in World War II with plague-infected fleas and cholera-coated flies and of the Americans during the Cold War with yellow fever-infected mosquitoes. With continued advances, defenses in the form of insecticides and vaccines meant that insects were no longer considered as battlefield weapons. However, in recent times sociopolitical changes have put insects back into the realm of human conflict through asymmetrical conflicts pitting combatants from nonindustrialized regions against forces from militarily and economically superior nations.

[Bioterrorism: data of a recent history of risks and uncertainties]. / Bioterrorismo: dados de uma história recente de riscos e incertezas.

Today, bioterrorism is a real threat in the whole world. Considering the actions of bioterrorism by using biological agents capable of promoting great epidemics and overload in the health systems of any city, state or country, the bioterrorism is not only a health professional concern, but government and military also. This article discusses a bibliographical review done in the LILACS, MEDLINE, SciELO and REPIDISCA databases, during the period of 1997 the 2007, the characteristics of related national publications to the bioterrorism, the type of biological agents studied, and the existing knowledge in the country to face a bioterrorism event, in order to feed with information the professionals who will act in first reply to the bioterrorism events and that are essential to reduce the number of victims.

Bioterrorismo: dados de uma história recente de riscos e incertezas / Bioterrorism: data of a recent history of risks and uncertainties

O bioterrorismo é hoje uma ameaça real em todo o mundo. Considerando-se que as ações de bioterrorismo utilizam agentes biológicos capazes de promover grandes epidemias e sobrecarga nos sistemas de saúde de qualquer cidade, estado ou país, o bioterrorismo passa a ser não apenas uma preocupação de governantes e militares, mas também dos profissionais da área da saúde. Este artigo discute, através de uma revisão bibliográfica, nas bases de dados LILACS, MEDLINE, SciELO e REPIDISCA, no período de 1997 a 2007, as características das publicações nacionais relacionadas ao bioterrorismo, o tipo de agentes biológicos estudados e o conhecimento já existente no país para fazer frente a um evento de bioterrorismo, a fim de subsidiar com informação os profissionais que irão atuar em ações de primeira resposta aos eventos de bioterrorismo e que são imprescindíveis para reduzir o número de vítimas.

Today, bioterrorism is a real threat in the whole world. Considering the actions of bioterrorism by using biological agents capable of promoting great epidemics and overload in the health systems of any city, state or country, the bioterrorism is not only a health professional concern, but government and military also. This article discusses a bibliographical review done in the LILACS, MEDLINE, SciELO and REPIDISCA databases, during the period of 1997 the 2007, the characteristics of related national publications to the bioterrorism, the type of biological agents studied, and the existing knowledge in the country to face a bioterrorism event, in order to feed with information the professionals who will act in first reply to the bioterrorism events and that are essential to reduce the number of victims.

Biological warfare agents.

Biological warfare agents are a group of pathogens and toxins of biological origin that can be potentially misused for military or criminal purposes. The present review attempts to summarize necessary knowledge about biological warfare agents. The historical aspects, examples of applications of these agents such as anthrax letters, biological weapons impact, a summary of biological warfare agents and epidemiology of infections are described. The last section tries to estimate future trends in research on biological warfare agents.

Ricin poisoning and forensic toxicology.

Ricin is one of the most fascinating poisons due to its high toxicity: as little as 500 microg can kill an adult. It gained fame by its use in the so-called 'umbrella murder' to kill the Bulgarian dissident Georgi Markov in 1978. Ricin also became known as a potential bio-terror agent to which people could be exposed through the air, food, or water. The origin, biochemistry, toxicity, and analytical procedures for the determination of ricin are summarized. The homicide of Markov is described as well as recent cases of criminal ricin use.