Bruce Gellin M.D., M.P.H.
National Vaccine Program Office
U.S. Department of Health and Human Services
Manufacturing Medical Countermeasures for Chemical, Biological, Radiological and Nuclear Threats: The Role of HHS
Committee on Appropriations, Health and Human Services, Education, and Related Agencies
Subcommittee on Labor
United States Senate
Friday August 21, 2009
Good morning, Sen. Specter and Rep. Altmire. I am Dr. Bruce Gellin, Director of the National Vaccine Program Office within the Department of Health and Human Services (HHS). I am honored to be here today to discuss this important topic, particularly in light of our ongoing challenges related to the 2009-H1N1 influenza outbreak. Vaccines are an important piece of our public health system and our medical countermeasure armamentarium, particularly against biological weapons. This morning I will provide a brief overview of HHS responsibilities for medical countermeasures development for chemical, biological, radiological and nuclear threats and then will focus more specifically on the topic of medical countermeasure manufacturing.
Medical Countermeasures – Development and Acquisition
Our progress in securing medical countermeasures begins with and depends on effective planning. The central framework for medical countermeasures planning and implementation in the Federal government is the HHS Public Health Emergency Medical Countermeasures Enterprise (PHEMCE), established in July 2006. This coordinated interagency group is led by the Assistant Secretary for Preparedness and Response (ASPR), and includes my office, the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), and the National Institutes of Health (NIH) as well as our partners from the Department of Defense (DoD), Department of Homeland Security (DHS), and Department of Veterans Affairs (VA). Through this Enterprise-wide effort, we are able to ensure that Federal activities with respect to needed medical countermeasures are effectively coordinated from research and development to acquisition and, ultimately, deployment. This supports a range of programs that I will briefly summarize for developing and acquiring medical countermeasures for man-made and naturally-occurring public health threats while building domestic manufacturing infrastructure.
The Biomedical Advanced Research and Development Authority (BARDA) within HHS's ASPR directs and coordinates the Department’s countermeasure and product advanced research and development activities. BARDA establishes systems that encourage and facilitate the development and acquisition of medical countermeasures such as vaccines, therapeutics, and diagnostics, as well as innovative approaches to meet the threat of chemical, biological, radiological and nuclear (CBRN) agents and emerging infectious diseases, including 2009-H1N1 influenza. BARDA provides an integrated, systematic approach to the development and purchase of the necessary vaccines, drugs, therapies and diagnostic tools for public health emergencies. It directs and coordinates the Department’s countermeasure and product advanced development activities and medical countermeasure domestic manufacturing infrastructure building, including strategic planning for medical countermeasure research, development, and procurement. This coordinated approach is critical to achieving success in the area of bioterrorism preparedness and has been proven through the recent H1N1 effort.
Specifically with respect to vaccines, HHS has a number of efforts underway. These efforts supported the first U.S. licensure of an avian influenza-based H5N1 vaccine in April 2007, which was highlighted by Time Magazine as the number one medical breakthrough of 2007. By the end of 2007, HHS had stockpiled 12 million courses of pre-pandemic H5N1 vaccine. However, maintaining a domestic production capability for these priority countermeasures is also an essential component of the pandemic influenza preparedness strategy. In May 2006, HHS awarded five contracts for over $1 billion to GlaxoSmithKline, MedImmune, Novartis (formerly Chiron), Solvay, and Dynport (with Baxter) for support of advanced development of cell-based influenza vaccines toward U.S. licensure and expanded domestic vaccine manufacturing surge capacity. In June 2007, we awarded two contracts for the retrofitting of existing domestic biological manufacturing facilities to produce egg-based influenza vaccines and included warm base operations for up to five years. Additionally, contract awards were made in 2008 for the construction of new domestic facilities for manufacturing cell-based influenza vaccines that is expected to quadruple the domestic pandemic vaccine manufacturing surge capacity by 2012.
A robust and groundbreaking advanced development program has led to the rapid maturation of modernized cell-based influenza vaccine production and antigen-sparing technologies. New combinations of adjuvants and products provided by multiple manufacturers are currently supported by performance-driven milestone contracts. More rapid vaccine production may be afforded by the development of next generation recombinant influenza vaccines, which HHS will support.
These investments enhanced our current capabilities to respond to the urgent needs for development and manufacturing of vaccine for use against 2009 H1N1 influenza. Currently, HHS has contracted with five companies that are now producing and conducting clinical trials or 2009 H1N1 vaccine for US supply (GSK, Sanofi, Novartis, CSL, and MedImmune).
Medical Countermeasure Analysis of Alternatives
In July 2008, Dr. Robert Kadlec, the then-Special Assistant to the President for Biodefense and Senior Director for Biodefense at the Homeland Security Council, requested that HHS and DoD conduct an Analysis of Alternatives:
“to identify the optimal facilities and operating model for addressing the gap in production and manufacturing of medical countermeasures against WMD [Weapons of Mass Destruction] threats in a manner that provides the best long-term value to the U.S. Government.”
It is important to highlight that the inspiration behind the development of such a biofacility is consistent with many of the broad goals articulated in the draft National Vaccine Plan (November 2008), especially regarding the objectives of
a. fostering advanced research and development toward new and/or improved vaccines that prevent diseases, including those that protect against emerging, re-emerging, and important Biodefense-related pathogens, and
b. improving access to appropriately designed pilot lot manufacturing facilities that produce clinical grade material for promising vaccine candidates. http://www.hhs.gov/nvpo/vacc_plan/2008plan/draftvaccineplan.pdf
As Dr. Kadlec noted, the timely availability of sufficient quantities of medical countermeasures “is essential for saving the lives of civilians and warfighters following a WMD attack.”
A principal mission of HHS and DoD is to provide medical countermeasures—drugs, vaccines, and therapeutics—to protect civilian and military populations, respectively, from attack with chemical, biological, radiological and nuclear (CBRN) agents. Developing sustainable medical countermeasures that are effective and readily available is an enormously complex task from a technical and organizational perspective.
Such medical countermeasures require:
- Discovery and early research
- Development and testing in surrogate animal models
- Advanced development through clinical trials
- FDA regulatory approval
- Production and manufacturing
- Stockpile supply management
- Distribution and dispensing strategies
- Stockpile replenishment
To accomplish the requested analysis, HHS and DoD commissioned an independent, third party study of vaccine manufacturing facility alternatives that should be considered. We will soon meet with our colleagues at DoD to discuss the findings and determine any recommendations that will be made in response to the request. But permit me to briefly share some general findings with you.
The focus of the analysis was on the advanced development, FDA approval and sustainment phases of the medical countermeasure lifecycle. Within the advanced development phase, the focus was only on advanced manufacturing process development. Sustainment refers to the storage, maintenance and replenishment of the active pharmaceutical ingredients and the dosage forms of medical countermeasures, as well as procurement, storage, and maintenance of required ancillary supplies needed to administer the countermeasure.
To date, the United States Government (USG) has successfully procured small molecule medical countermeasures (e.g., drugs) from established contractors, and the analysis determined that there is excess industry capacity available for manufacturing these types of products. Thus, the current process of contracting with industry to produce ‘small molecule’ medical countermeasures appears to be viable now and in the future.
Together, HHS and DoD have stated requirements for a collective portfolio of 23 large molecule CBRN medical countermeasures that are biologically-based products. Past analyses have recommended that the USG own and manage a production facility for the manufacture of large molecule products (e.g., vaccines, monoclonal antibodies) to increase control of the approval and supply processes in order to minimize risk of supply disruption.
Since the biopharmaceutical industry, as a whole, has not traditionally developed medical countermeasures for the US Government, there is a perception that large gaps exist in manufacturing and production facilities. However, recent history shows that both HHS and DoD have successfully contracted with emerging biotechnology innovators and contract manufacturers for advanced development and procurement of medical countermeasures. Moreover, some USG contractors are investing heavily in production facilities, the majority in the United States, further addressing the facilities gap.
The analysis suggests that the US Government should increase its capabilities to oversee the advanced manufacturing process development and supply programs to ensure that,
- needed medical countermeasures achieve FDA approval, and
- there is an ongoing supply of the product.
Alternative Scenarios Examined
Three alternative scenarios for the development, approval, manufacturing, and sustained replenishment of large molecule medical countermeasures were examined using both quantitative and qualitative criteria.
- The first alternative examined was continuing the existing process of contracting the development and manufacture of medical countermeasures.
- The second alternative examined was continuing the existing process while strengthening technical, quality/regulatory, and sourcing/supply capabilities; and contracting with additional manufacturers of bulk active product ingredients and formulation, filling, and finishing. This alternative also provides for enhanced access to process development and manufacturing capabilities.
- The third alternative is one that has been proposed in previous studies. It calls for the Government to manufacture all needed medical countermeasures. This approach, which includes establishing a new public-private partnership, anticipates a fully dedicated manufacturing facility for all medical countermeasures under control of the US Government.
The first alternative only satisfies the need of the USG to a limited degree because, although the US Government has been successful in developing and manufacturing some medical countermeasures, it does not provide the USG with the most effective and efficient processes for managing the potential growing number of highly complex medical countermeasures. While this alternative is the least costly of the three alternatives, it provides the fewest capabilities and carries the risk of less than optimal oversight to ensure the manufacturing capability for the growing medical countermeasure supply chain.
The second alternative builds on the successful current USG medical countermeasure contractual approach and enables flexible decision making for advanced manufacturing process development, stockpiling, backup, and surge. It expands current capabilities to meet the complexity and urgency of medical countermeasures yet to be developed and scaled to manufacturing requirements. This alternative offers the lowest operational risk to achieve current requirements of all the alternatives by creating a collaboration of US Government and a network of incentivized, highly specialized, and knowledgeable industry suppliers. It enables future operations to be enhanced most efficiently by incorporating dedicated technology, quality and regulatory compliance, and sourcing and supply functions. In addition, contract manufacturing is less costly and timelier than constructing and operating a dedicated facility.
Of all alternatives examined, the third alternative potentially has the highest risk of supply chain failure and, compared to the two other alternatives, carries the highest cost. In addition, the time required to develop reliable systems for long-term, full-scale manufacture of biologics (large molecules) could impede progress toward needed FDA approval. This alternative also does not provide sufficient surge or backup capabilities. Finally, only a few, if any, biopharmaceutical companies have clustered the production of so many products in a single facility. An adverse regulatory decision or a catastrophic event could shut down the single facility. A single facility with many products is more complex to manage, and is more likely to trigger an adverse regulatory decision than a network of specialized manufacturers.
HHS is committed to protecting the health and safety of American citizens from CBRN threats. Along with our colleagues at DoD, HHS is committed to a full examination and discussion of all viable options for the manufacture of vaccines and other medical countermeasures against identified threats.
We appreciate your support and continuing interests in this important area. I am happy to answer any questions.
Last revised: June 18, 2013