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response to enable collaborative and noncontradictory efforts and produce consistent risk messages to the public.58 Collaboration and communication between private and public sectors has been highlighted in multiple reports and reviews as a key area in need of improvement. Medical Countermeasures and Pharmaceutical Interventions The availability of safe and effective medical countermeasures (MCMs) will greatly enhance our abilities to respond to a high-impact respiratory pathogen. During such events involving high-impact respiratory pathogens, the availability of MCMs (ie, vaccines, 51 therapeutics, diagnostics, and other medical supplies such as personal protective equipment, or PPE) represent our best opportunities to limit morbidity, mortality, and disease transmission. Vaccination is the single most effective pharmaceutical intervention and would likely be the preferred MCM in a high-impact respiratory pathogen outbreak because it can typically prevent infection in individuals and limit transmission in populations. Antivirals and other therapeutics like monoclonal antibodies, if available to treat the ill, might be of great clinical value, and, in some cases, if there were sufficient supplies of these products (seemingly unlikely in most places under current conditions), they could serve as prophylactic agents. PPE, including masks and respirators, would also play a critical role in infection prevention and control, particularly if no vaccine or therapeutics are immediately available.110 The ability of MCMs to alter the course of a high-impact respiratory pathogen would depend on the effectiveness, timeliness, and efficiency of a complex system that starts at basic discovery and ends at the treatment or prevention of illness (see Table 2). In between, national and local governments, academic institutions, the pharmaceutical industry, and the private sector would need to move products through early and advanced development and the regulatory process, the manufacturing and finishing processes, and the distribution and dispensing systems needed to administer countermeasures to people who need them. From an MCM perspective, global capacity to respond to pandemic influenza is likely to be far stronger than it would be for any other novel high-impact respiratory pathogen, given that annual epidemics of seasonal influenza create a sustainable market for vaccines and antivirals that may be able to be adapted for use in the event that a pandemic strain emerges. However, even in that case, very few countries have the capability to develop and distribute MCMs in time to have an epidemiologically meaningful impact on the course of a pandemic. For example, in 2009, the peak of the H1N1 influenza pandemic passed before a vaccine was widely available. Table 2: Making and Using Drugs and Vaccines Activities* Primary Actor Basic discovery Academia and industry Early development Academia & industry Advanced development Industry Manufacturing and production Industry Distribution Public or private logistics Dispensing or administration Public health; health care; pharmacies; perhaps community organizations? Perhaps self-administration, if future technologies and approaches allow? *Sources of funding for these activities comes predominantly from governments, foundations, international organizations, and industry. 52 If the high-impact respiratory pathogen is not influenza, then the prospects around MCM development would be far more dire, as MCMs are likely to be much less far along in development—if in development at all. In the case that an existing vaccine candidate has been developed (eg, perhaps a coronavirus vaccine for an existing coronavirus could be used with some value for a novel coronavirus that causes high-impact respiratory outbreak), there is likely to be no surge manufacturing plan or capacity. If the pathogen is completely novel and there is no existing research base—what WHO refers to as a Disease X scenario—there is no alternative but to start with fundamental science and then advance MCMs through the development pipeline as quickly as possible. Given existing approaches, technologies, and policies, vaccine development takes an estimated 15 years and costs approximately $1.4 billion (see Box 7).111-114 Attempts at developing vaccines against respiratory pathogens such as SARS coronavirus have been slow. Technical barriers at the discovery and R&D phases of development or market failures can be rate limiting. Once a candidate drug or vaccine has been developed, it must then go through clinical trials to test for safety and efficacy. However, as was demonstrated in the 2014-2016 Ebola epidemic in West Africa, trials in the midst of an outbreak will be logistically and ethically challenging. Moreover, many countries maintain their own paradigm for pharmaceutical regulation and have not put in place policies for emergency use of medical countermeasures that may not have full regulatory approval. These complexities could slow international MCM deployment, which could impede efforts to control a severe disease outbreak. During the 2009 influenza pandemic, according to former US Ebola Response Coordinator Ron Klain, “thousands of doses of vaccine sat in warehouses because of a lack of an internationally accepted process to approve and administer it, and to compensate individuals who might be harmed by it.”115 In current conditions, manufacturing would be a critical bottleneck in the MCM response to a novel respiratory pathogen. The bulk of our manufacturing capacity for vaccines exists in a handful of large pharmaceutical companies in only a few countries. Further, those companies have optimized their manufacturing output based on the projected demand for their products, which means there is very little surge capacity in the system. Companies would be faced with taking commercial vaccine production offline in order to accommodate vaccine for the new pathogen. Also, manufacturers may face political pressure to produce vaccine for their home country before exporting to the rest of the world. This could mean that only a few countries have access to MCMs until manufacturing could be significantly expanded, which could be months or even