BARDA Core Services provides direct support to our Partners as we work together to develop medical countermeasures
The PHEMCE MCM Review (2010) recommended that PHEMCE partners provide not only financial help to medical countermeasure developers but also technical and regulatory assistance. BARDA’s Strategic Plan (2011) set a goal to provide assistance to developers through core assistance programs in critical areas including animal and clinical studies to obtain safety and efficacy data and manufacturing optimization, validation, and scale-up for clinical studies and commercial launch.Read More
The mission of the Biomedical Advanced Research and Development Authority (BARDA) is to develop medical countermeasures that address the public health and medical consequences of chemical, biological, radiological, and nuclear (CBRN) accidents, incidents and attacks, pandemic influenza, and emerging infectious diseases.
In 2011 BARDA established the Non-clinical Studies Network comprised of 17 laboratories in the U.S. and UK that have perform studies supporting the natural history of chemical, biological, radiological, and nuclear events in multiple animal models and the safety and efficacy afforded by different medical countermeasures supportive of FDA Approval. The Centers for Innovation in Advanced Development and Manufacturing (CIADM) were established in 2012. The three Centers are located in the U.S. and are comprised of industry, academic, and Sate government entities partnered with BARDA. BARDA established in 2013 a Fill Finish Manufacturing Network (FFMN) to assist medical countermeasure developers with final drug product manufacturing (e.g., aseptic syringe and vial filling, lyophilization), support national pandemic influenza vaccine manufacturing efforts and other public health emergencies. The FFMN is comprised of four domestic manufacturers with a broad set of capabilities to address every day and emergency needs. Lastly BARDA established a Clinical Studies Network (CSN) in 2014 to provide clinical study services from designing clinical protocols to managing clinical trial sites. The five domestic Clinical Research Organizations in the Clinical Studies Network will provide these services to medical countermeasure developer partnered with BARDA and backfill NIH’s clinical study capabilities in a public emergency as requested.
Together the four existing BARDA core service assistance programs form a comprehensive aid package to mitigate many inherent risks associated with medical countermeasure development and manufacturing.
Core Services currently offered through BARDA that support medical countermeasure (MCM) development and manufacturing activities are as follows:
Select a service area to learn more
In 2012, BARDA launched an innovative program to strengthen domestic manufacturing by establishing three 'Centers' to develop and manufacture medical countermeasures, such as vaccines and therapeutics needed to protect health in emergencies, and transition quickly and cost-effectively between different products. Created as public-private partnerships by the Department of Health and Human Services (HHS), the Centers for Innovation in Advanced Development and Manufacturing (CIADMs) were designed to provide a significant domestically-based infrastructure capable of producing medical countermeasures, or MCMs, to protect Americans from the health impacts of bioterrorism as well as pandemic influenza and other disease in response to public health emergencies.
As public-private partnerships, the HHS’ 2012 CIADM network aimed to bring together the innovative ideas of small biotech firms, the training expertise of academic institutions, and the development and manufacturing experience of large pharmaceutical companies. The goal of the 2012 program was to ensure a sustainable domestically-based MCM infrastructure with unprecedented ability to accelerate the development and manufacture of MCMs in time of need. A key objective of the Centers was to explore emerging and innovative technologies that HHS could apply to current or future medical countermeasures to reduce development risk, increase product yield, and ultimately to reduce total life-cycle costs through flexible manufacturing, the consolidation of costly product development expenditures, or other economy-of-scale opportunities.
The program supported successful investment in U.S.-based manufacturing capacity, including retrofitting existing facilities and building new facilities t incorporated flexible, innovative manufacturing platforms able to manufacture multiple products. These facilities were designed to use modern cell- and recombinant-based vaccine technologies with the potential to produce vaccines for pandemic influenza and other threats more quickly and economically.
WHO WERE THE 2021 CIADM PARTNERS??
WHAT INFORMED THE ESTABLISHMENT OF THE CIADM?
Establishing the centers achieves a core recommendation cited in the 2010 Public Health Emergency Medical Countermeasure Enterprise Review; a comprehensive, government-wide review called for by Secretary Sebelius to address challenges encountered in developing biodefense medical countermeasures. These centers also address concerns raised by the President's Council of Advisors on Science and Technology in the August 2010 Report to the President on Reengineering the Influenza Vaccine Production Enterprise to Meet the Challenges of Pandemic Influenza (PDF - 60KB), which called for flexible, nimble, and modern vaccine manufacturing technologies.
Since 2012 HHS has completed support of activities to retrofit and upgrade the manufacturing capacity at CIADM sites, increasing US-based capacity. HHS is actively engaging with one remaining CIADM partner. Like most innovative efforts, the CIADM program and the 2020 COVID-19 response provided important insights on how HHS can better invest in expanding manufacturing capacity and capability. These events have guided and informed the direction of the new National Biopharmaceutical Manufacturing Partnership (BioMaP) jointly led by BARDA and the U.S. Department of Defense (DoD).
To help the country build manufacturing capabilities needed to produce population-scale vaccines and therapeutics, BARDA (under the BioMaP initiative) released in November 2021 a Request for Information (RFI) to gain industry feedback to assemble a next-generation manufacturing capabilities network that leverages consortiums of partners to sustain U.S.-based MCM manufacturing capacity overtime and fortify our preparedness against further public health threats, such as pandemic influenza and emerging infectious diseases. BARDA will continue to look for new opportunities to partner with industry, build on lessons learned from our prior and existing partnerships, and work with industry to strengthen U.S.-based MCM manufacturing capacity and capability.
In 2010,HHS Secretary Kathleen Sebelius released a comprehensive review (PDF - 336 KB) of the nation's public health emergency medical countermeasure enterprise after private industry and the federal government faced challenges with 2009 H1N1 vaccine production. Among other barriers, the analysis revealed that current vaccine manufacturers lacked the capacity to rapidly fill vaccine vials and finish packaging vaccine in sufficient quantities for the nation. The review recommended creating a network of existing, pre-qualified facilities that could fill and finish the vaccine for manufacturers in a public health emergency.
The nation's pandemic influenza vaccine manufacturing capacity grew in 2012 when HHS established three Centers for Innovation in Advanced Development and Manufacturing to develop and manufacture medical countermeasures, such as vaccines and medicines used to protect health in emergencies. Among other capabilities, the CIADMs are designed to be able to manufacture 150 million doses of vaccine within 12 weeks of the declaration of a pandemic, supplementing our existing influenza manufacturing capacity. The FFMN similarly supports the increase in our existing influenza manufacturing capacity.
On September 27, 2013, the 4 Fill Finish Manufacturing Network (FFMN) original contracts were awarded to Cook Pharmica (Bloomington, IN), Patheon Pharmaceuticals (Greenville, NC), Par Pharmaceuticals (Rochester, MI) and Nanotherapeutics (Alachua, FL). In September 2016, two additional contracts were awarded to companies that can also provide cores services as well as specifically provide Live Virus Vectored (LVV) fill and finish services: Advanced BioSciences Laboratories, Inc. (ABL) (Rockville, MD) and IDT Biologika Corporation (Rockville, MD). Today's enhanced Fill and Finish Manufacturing Network will complement the CIADMs and manufacturers, and support the availability of an additional 117 million doses of influenza vaccine in the event of a pandemic. Additionally, as a component of the National Medical Countermeasure Response Infrastructure, the network is fully prepared to support any response efforts against future emerging infectious diseases or other public health emergencies.
The expanded fill and finish manufacturing network also could provide core services for drugs and vaccines used to protect health in emergencies caused by chemical, biological, radiological and nuclear threats. These companies have proven expertise in:
The Pandemic and All-Hazards Preparedness Act of 2006 specified that among the duties of advanced research, development, and procurement of qualified medical countermeasures was the design and development of tests or models, including animal models, for such testing.
The development of animal models is a key element in the successful development of medical countermeasures for CBRN, influenza, and emerging infectious agents. The efficacy of products against most of these threats could never be verified using traditional clinical studies. In 2002, the FDA amended its regulations for drugs and biologics to permit approval or licensure of medical countermeasures based on substantial evidence of effectiveness in animals when adequate and well-controlled efficacy studies in humans cannot be conducted because it would be unethical to expose healthy human volunteers to lethal or disabling agents, and relevant field efficacy trials in humans are not feasible. This change in the regulations commonly referred to as the "Animal Rule," made the design and conduct of adequate efficacy studies in appropriate animal models of paramount regulatory importance, since the inference of efficacy in humans is based on efficacy data derived in animals.
In May 2011,BARDA awarded multiple contracts to establish the Nonclinical Development Network and facilitate development and qualification of animal models in support of the chemical, biological, radiological and nuclear countermeasures in BARDA's portfolio. The goals of the program are:
The animal studies program is a component of BARDA's core services and is available to all of the operational teams within BARDA-CBRN, Influenza and Emerging Infectious Diseases. Areas of focus thus far, include animal model development for Burkholderia psudomallei, Burkholderia mallei Francisella tularemia, hematopoietic acute radiation syndrome, and cyanide ingestion.
View the Animal Model Network contract awardee map (PDF - 163KB).
The BARDA Strategic Plan (2011-2016) set forth a goal to provide enabling core assistance services to aid medical countermeasure (MCM) developers with essential product development tools and services. Part of the strategy was BARDA’s establishment of a Clinical Studies Network that can provide comprehensive (Phase 1-4) clinical study services to help evaluate the safety, dosage, pharmacokinetics/pharmacodynamics and efficacy of MCM candidates. In 2014, BARDA created its CSN by partnering with five (5) Contract Research Organizations including TRI, ClinicalRM, Emmes, Rho and PPD.
The CSN became immediately engaged in the Ebola Response in 2015 as part of BARDA National MCM Response Infrastructure. The CSN worked with CDC, the Sierra Leone Ministry of Health, and the Sierra Leone College of Medicine and Allied Health Sciences to conduct the Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE). The STRIVE study began enrolling healthcare workers and other front line workers in April, 2015, and over 8,000 subjects received an investigational vaccine to prevent Ebola. The study will assess the safety and immunogenicity of the vaccine. BARDA’s CSN is providing staff training, clinical site development and monitoring, and data management, biostatistics, safety, cold chain, and logistics support.
In March, 2016, the CSN launched BARDA’s first sponsored trial, the BARDA Ready in Times of Emergency (BRITE) study, evaluating safety and immune responses of H5N1 pre-pandemic influenza vaccines and adjuvants that have been stored in the national stockpile for up to 10 years. The study is being conducted at 6 US sites selected in part because of their proximity to poultry farms or research laboratories in order to target workers at higher risk of exposure to avian influenza. The results of this study are expected to inform future decisions on the length of time pre-pandemic influenza vaccines and adjuvants maintain their activity and are safe to store in the National Pre-Pandemic Influenza Vaccine Stockpile in order to help protect the US population.
The CSN also worked with BARDA’s Chemical MCM Program to compile data for a supplemental FDA New Drug Application for midazolam (an anticonvulsant drug) administered by auto-injector to treat neurotoxin-induced seizures. BARDA-supported FDA approval of intramuscular midazolam for emergency treatment of prolonged seizures in children and adults will ensure that this vital MCM is widely available to first-responders.
The CSNplans in 2016-2018 to conduct additional clinical studies linked to BARDA’s areas of investment, including heterologous prime boost studies of different influenza vaccines in the National Pre-Pandemic Influenza Vaccine Stockpile, studies of an anthrax vaccine for an elderly population, and studies of candidate therapies against MERS-CoV infection in the Middle East. In conjunction with partner programs in the National MCM Response Infrastructure, these activities will increase BARDA’s readiness to respond to biothreats and public health emergencies.
Clinical Studies Network contract awardee map (PDF - 160KB)
The Division of Regulatory and Quality Affairs is a core service within BARDA providing strategic opinions on quality and regulatory issues to ensure safe and effective medical countermeasures. RQAsupports product development, from contract pre-awarding stage throughout product approval by providing the following services:
Collaboration with Product Coordination Teams within BARDA, other Federal Agencies, and product developers to support medical countermeasure programs in each stage of product development and FDA submission. This collaborative effort enables quick and appropriate regulatory solutions to keep with project timelines.
Staying up to date with industry practice and FDA guidance to provide all stakeholders with current regulatory and quality advice.
Involvement with many cross-functional activities such as source selection, pre/and post-award site visits, quality audits, contract negotiation, production, acquisition, storage, and use. The division ensures product integrity and compliance during the storage life cycle in the National Strategic Stockpile.
Providing support to companies in selection of subcontractors, such as laboratories or manufacturing sites and ensuring that quality systems at all contract and subcontract facilities align with FDA regulations.
Production and facilitation of documents that enable end users to use products safely via Investigational New Drug (IND) Applications and Emergency Use Authorizations (EUA) for unapproved medical countermeasures or an unapproved use of an approved medical countermeasure needed in a declared public health emergency.
Click here for a list of relevant guidances for FDA regulatory review.