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Testimony

Statement by
Jesse Goodman  M.D., M.P.H.
Director Center for Biologics, Evaluation and Research
Food and Drug Administration
U.S. Department of Health and Human Services

on
H1N1 Preparedness: An Overview of Vaccine Production and Distribution 

before
Committee on Energy and Commerce
Subcomittees on Health, and Oversight and Investigations
U.S. House of Representatives


Wednesday November 18, 2009

INTRODUCTION

Chairman Stupak, Chairman Pallone, and Members of the Subcommittees, I am Dr. Jesse L. Goodman, Chief Scientist and Deputy Commissioner for Science and Public Health (Acting) at the Food and Drug Administration (FDA or the Agency).   I appreciate the opportunity to be here today to describe the role of FDA in our nation’s response to the H1N1 influenza pandemic.

When the 2009 H1N1 influenza virus emerged in the spring, FDA established an incident command system to speed and coordinate our response and to facilitate collaboration with and outreach to our external partners.  The Agency created teams to address vaccines, antivirals, diagnostics, personal protection, and consumer protection.

This approach allowed us to work hand in hand with our sister agencies within the Department of Health and Human Services (HHS), including the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), the Office of the Assistant Secretary for Preparedness and Response (ASPR), as well as other offices and colleagues within the Department, to help rapidly mobilize the public health emergency response.  I am pleased to provide updates in each major area of FDA activity, as well as the challenges of the present and future.

Vaccines

FDA’s vaccine team has worked with our sister HHS agencies, other U.S. government agencies, the World Health Organization (WHO), foreign governments, sister regulatory agencies, and vaccine manufacturers to facilitate the development, production, and availability of safe and effective vaccines against the 2009 H1N1 virus.  While vaccines were made, licensed, and delivered to people in record time, the amounts of vaccine available to date are substantially less than had been expected, primarily because the virus is not growing as well or yielding as much vaccine as forecast.  While we are frustrated that more vaccine is not now already available, everyone engaged in this effort—government and industry—has done and is doing everything possible to get as much vaccine to people as quickly as possible and to help close the gap between demand and supply.  This includes continuing to work with the HHS Office of the Assistant Secretary for Preparedness and Response’s (ASPR) Biomedical Advanced Research and Development Authority (BARDA) and with manufacturers to successfully increase vaccine yield as well as production capacity including, for example, bringing on board several additional manufacturing lines to fill and finish vaccine.  These and other collaborative efforts have helped the continuing increase in vaccine production and availability.  An important perspective is that the entire world is struggling with the biology of this virus and the challenge of reduced manufacturing yields and that the United States, thanks to a rapid response and public-private collaboration, has been one of the first countries to mount an immunization campaign with substantial availability of millions of vaccine doses.

At the same time that many are seeking the vaccine, and as more individuals are immunized, many people have asked how FDA and the scientific community can have confidence in a vaccine produced so quickly for a disease so new.  The answer is straightforward:  the vaccines FDA has approved are made with a method that is tried and true.  This method rests on a strong scientific foundation and a tremendous amount of experience.  Each year, FDA and vaccine manufacturers follow a series of steps to make a new influenza vaccine targeted to the three main circulating strains of influenza. These steps have produced a very safe vaccine time and again, adding up to hundreds of millions of doses administered in the United States.  We followed this same scientific and regulatory approach for the 2009 H1N1 vaccine.  Throughout all of this effort, FDA, CDC, NIH, ASPR, and vaccine manufacturers have worked together intensively to do all that is possible to speed vaccine production and availability.

I will briefly summarize each of the key steps.

First, within weeks of the very first cases appearing in April scientists modified the 2009 H1N1 virus into versions suitable for producing a vaccine.  For each year’s seasonal influenza vaccine, this step is an ongoing process that occurs in laboratories around the world, including FDA’s, in conjunction with surveillance to identify new influenza virus strains that might pose a public health threat.  For the 2009 H1N1 virus, strains needed for vaccine manufacturing were created and provided to manufacturers in the last week of May 2009.

Second, companies began to grow the vaccine strain in specially produced chicken eggs.  As recently as a few years ago, eggs would not have been available in the summer, and vaccine production would have been substantially delayed.  Fortunately, this year, thanks to your support and the investments by HHS in pandemic preparedness, manufacturers immediately could tap into a reserve supply of eggs made by additional flocks of chickens.  These flocks were available under contracts put in place by ASPR for just this purpose—to prepare to respond to a possible pandemic.  To incubate the eggs and make vaccine, companies used facilities specifically inspected and licensed by FDA for influenza vaccine production.  

Similarly, investments in pandemic preparedness by Congress and work by ASPR and FDA mean that we have more licensed manufacturers and more production capacity.  For example, in May, FDA licensed additional manufacturing capacity at Sanofi Pasteur’s Swiftwater, Pennsylvania, facility: capacity that is now playing an important role in providing vaccine to our nation.  While we clearly need much more capacity in both the United States and globally, without the investments of the past several years, and our ongoing efforts, the current situation would be far more challenging.

Third, we sought outside input from experts and the public.  At the end of July, FDA convened a public meeting of its expert vaccine advisory committee to review the Agency’s approach to approval of the 2009 H1N1 vaccines.  This committee includes scientists, physicians, public health officials, and a consumer representative.  The committee supported making the vaccines the same way and holding them to the same standards used every year for the seasonal influenza vaccine.

Fourth, we developed and then provided manufacturers with reagents and tests needed to measure the vaccine’s potency—a step essential in manufacturing.  Scientists from the United States, United Kingdom, Australia, Japan, and other nations, working together with WHO, developed these tests to assure the proper amount of influenza antigen goes into each dose of vaccine to induce an antibody response, thus providing protection against disease caused by strains included in the vaccine.  This is an essential step before final vaccine production can be completed. 

On September 15, after reviewing applications from manufacturers similar to those submitted each year for licensed seasonal vaccine, FDA licensed four vaccines against the 2009 H1N1 influenza virus.  A fifth vaccine was licensed last week.  FDA found that all of the standards to ensure the safety and potency of these vaccines had been met. 

Over the summer, NIH and vaccine manufacturers initiated clinical trials to determine the optimal dosage and number of doses needed to induce a protective immune response.  These trials have helped both the U.S. and the world understand H1N1 vaccines and how best to use them.  Just as for seasonal vaccine, one dose of unadjuvanted H1N1 vaccine induces a robust immune response likely to be protective for adults and older children.  For younger children, two doses of the H1N1 vaccine will likely be optimal, also as seen with seasonal vaccines.  No serious safety problems attributable to the vaccine have emerged during the trials, which have so far included over 3,600 subjects at NIH-supported institutions alone.

We are not taking anything for granted.  We subject the 2009 H1N1 influenza vaccines to the same stringent manufacturing and quality oversight processes that are in place for seasonal influenza vaccine.   FDA inspects these plants at least once a year to assure that quality controls are followed at every step in the production process.  Each facility also is inspected annually for compliance with FDA’s current Good Manufacturing Practices.  Extensive in-process quality control and product testing (such as for potency and purity) are required at multiple stages of the manufacturing process.  No lot of the 2009 H1N1 vaccine can be used until it has been fully tested and released as sterile and potent by both the manufacturer and by FDA.  While we expect these vaccines to have the same excellent safety profile as seasonal influenza vaccines, CDC and FDA are collaborating with both multiple U.S. partners and our global counterparts to build a markedly enhanced safety monitoring system that utilizes data available across U.S. Government agencies and in the health care system, as well as globally, to look for any unexpected, rare, serious adverse events and to quickly investigate concerns.   Should any safety concerns arise, we will evaluate them thoroughly and bring them quickly to public attention. Again, collaboration across the public and private sector has been unprecedented.  These efforts also will strengthen and inform future safety monitoring efforts for vaccines as well as other products

Antiviral Products

An effective response to H1N1 must involve a full range of prevention and treatment.  FDA’s antiviral team has worked hard to facilitate the availability of antiviral medications for ill patients in the United States.  Fortunately, to date, the 2009 H1N1 virus has generally been sensitive to the FDA-approved antiviral drugs, Tamiflu® and Relenza®.  On April 27, 2009, FDA issued two Emergency Use Authorizations (EUAs) that authorize additional circumstances in which those medicines can be used to treat illness caused by the 2009 H1N1 influenza virus.   These authorizations were utilized by CDC and state and local partners to speed and extend access to these medications to patients in need of treatment all over the country.  FDA’s work on dosing of Tamiflu in children less than 1 year of age was adopted by countries around the world.  Since that time, the antiviral team has worked to authorize the use of needed antiviral drugs through several creative and effective public health actions.

FDA has worked with ASPR and with manufacturers to do everything possible to speed additional production of Tamiflu and Relenza.  The public/private interaction has been very positive and manufacturing continues at high volume.  All current manufacturing capacity is being fully utilized and, as has been the case for vaccine production, FDA stands ready to perform priority review of any additional manufacturing capacity industry can bring on line.

FDA determined through scientific review and analysis of available data by FDA scientists that certain lots of Tamiflu and Relenza can be safe and effective when used beyond their expiration dates.  As a result, for this emergency, FDA authorized the appropriate use of large amounts of antiviral medications that may otherwise have been thrown away because it was beyond its labeled expiration dates, thus helping prevent shortages and keeping needed medicines available for patients.  FDA also recently extended this EUA authorization to include these drugs in the possession of the private sector, keeping businesses and health care delivery systems around the country from having to throw out medication that FDA has determined is still acceptable for use beyond its expiration dates.

While Tamiflu capsules and inhaled Relenza remain in good supply, in part due to these measures, we also recognized the potential for shortages of Tamiflu and Relenza products, particularly of the Tamiflu for Oral Suspension (liquid Tamiflu used to treat young children who cannot swallow pills).  Working with manufacturers, we provided guidance for pharmacists to enable them to mix Tamiflu from capsules with syrups, to make a compounded version of liquid product for children under emergency circumstances, when supplies of oral suspension are otherwise unavailable.  Since the emergence of the 2009 H1N1 influenza virus, FDA and CDC have worked together to provide a series of outreach communications to help ensure that pharmacies are familiar with this option.  Many pharmacies large and small, including major chains, such as Walmart and Walgreens, have stepped up to meet this need, and their pharmacists will make a liquid Tamiflu formulation, as needed.  Recently, after receiving suggestions from our partners, FDA updated its communications to make the compounding process more efficient in situations where multiple prescriptions are being filled.

Further, FDA has closely tracked shortage reports for antiviral drugs, working with the medical community and hospitals to identify areas that are in greatest need of supplies.  Currently, there are no approved intravenous influenza antiviral medications.  Access to intravenous antivirals is extremely important for critically ill patients who may not be able to take or absorb oral or inhaled dosing forms, or in whom intravenous administration is the only dependable route.  ASPR has been supporting the development and production of intravenous antiviral medicines to help meet this need.  These include peramivir, a medication similar to Tamiflu in how it keeps the influenza virus from growing.  Peramivir is not yet an approved drug and is still undergoing assessment of its safety and effectiveness in clinical trials.  On October 23, 2009, working closely with CDC, and after careful evaluation of available data from clinical studies to date and from emergency treatment, FDA issued an EUA for peramivir intravenous (IV), facilitating its use and availability to appropriately treat certain adult and pediatric patients with confirmed or suspected 2009 H1N1 influenza infection who are admitted to a hospital. 

In Vitro Diagnostics

When the outbreak began, there were no laboratory tests available that could accurately diagnose infection with the 2009 H1N1 virus.  Existing rapid influenza tests are not reliable for this H1N1 virus, and to date no test has been cleared or approved for the diagnosis of 2009 H1N1 influenza virus.  CDC mobilized quickly to produce a test for use in laboratories with suitable expertise, and FDA worked with CDC to rapidly evaluate the test and issued an EUA on April 27, 2009, making testing available to a wide network of public health and other qualified laboratories very soon after the start of the outbreak, a remarkable accomplishment.  Since that time, FDA has worked with others in both government and the private sector to increase the availability of reliable testing for 2009 H1N1 influenza under EUAs.  Nine EUAs have been issued for H1N1 laboratory tests, including one to the Department of Defense on August 24, 2009, using rugged equipment that allows for testing in remote areas including near combat.  Recently FDA published guidance intended to provide information on the types of data developers should submit in a request for an EUA for a test intended to diagnose H1N1.

Personal Protective and Other Medical Equipment

FDA has worked with CDC, ASPR, manufacturers, and others to increase production and availability of personal protective equipment such as gloves, masks and respirators, and to enhance the supply chain of equipment needed for respiratory and intensive care.  On April 27 of this year, FDA authorized an EUA for 15 different N95 disposable respirators, allowing for emergency use of these respirators in our national stockpile.

Protecting the Public from Fraudulent Products

Unfortunately, many people are seizing on the 2009 H1N1 influenza pandemic as an opportunity to make fraudulent claims and promote fraudulent treatments to the public.  Many of these deceptive products are being sold over the Internet through illegitimate Web sites, and prey on consumers’ desires to protect themselves and their families.  These products come in all varieties and include dietary supplements or other food products, as well as products purporting to be drugs, devices or vaccines that prevent or treat illness caused by the H1N1 virus.  If vulnerable patients purchase these fraudulent products and delay or avoid treatment or vaccination, tragedy could result.

FDA anticipated these risks and established the 2009 H1N1 Consumer Protection Team that has put in place an aggressive strategy to combat fraudulent 2009 H1N1 products.  It has been active in protecting the public by identifying fraudulent products and following up with enforcement actions, as appropriate.  The team has sent over 75 official warnings to more than 80 Web sites, covering about 140 different products, and has given Web site owners 48 hours to respond.  Currently, FDA’s warnings have resulted in a compliance rate of 85 percent.

Since May 2009, the Agency has issued four press releases to alert the public about fraudulent products.  Fraudulent products targeted and subject to warnings from FDA, range from shampoos, soaps, solutions, and sprays claiming to be scientifically proven to kill the 2009 H1N1 influenza virus—to power immune drops that claim to exterminate the virus from one’s body—to a test that claims it can detect the virus—to products that claim to be safer, more effective, natural alternatives to the 2009 H1N1 influenza vaccine.  Products purporting to be Tamiflu or other antiviral drugs may be contaminated, contain impure, unknown, or ineffective ingredients, or only contain aspirin.

The nature of the Internet means that often, as soon as one site comes down, another replaces it. 

We know that as long as public health threats exist, there will be those who will try to exploit the fears of consumers.  The public should know that if a product seems too good to be true, it probably is.  To help, we have put an easily accessible list of fraudulent products on our Web site as well as provided a widget that anyone can download to their own Web site to help spread the word.  We will remain vigilant and ask consumers to do the same.   

Looking Ahead

Much has been accomplished in a very short time by the strong collaborative efforts of those working inside and outside our government.  While we are facing this public health challenge, we should ask and are asking ourselves, even in the midst of it, what can we learn to do better, both now, as we respond, and for the future?

First, even though the first vaccines became available quickly, using tried and true egg-based technologies, we need much more capacity, both in the United States and globally, to produce them.  In the United States, major investments are underway in advanced vaccine development and manufacturing capacities, which include vaccines manufactured in cell culture systems.  FDA has provided guidance to manufacturers to help ensure that cell culture-based vaccines can be made safely.  In addition, we are supporting the development and use of recombinant and other newer technologies that offer the potential to serve as “platforms” for more rapid development, production, and deployment of vaccines against new influenza viruses or other emerging public health threats.  These approaches may offer a number of advantages in scalability, reliability and speed.  Such efforts are ongoing and, with your support, must both continue and be augmented.

Second, HHS is funding the development and careful evaluation of adjuvanted influenza vaccines.  Adjuvants are substances added to vaccines that are intended to help boost the immune response.  There are instances in which adjuvanted influenza vaccines may be needed or desirable, for example, when the vaccine cannot induce an adequate protective immune response without them, or to potentially help broaden the immune response to address dramatic shifts in strains that might occur as an outbreak evolves.  Currently FDA-licensed influenza vaccines do not contain adjuvants.  However, both NIH-based and HHS-supported industry-based studies are underway, including with the 2009 H1N1 virus, that are increasing the information available on the safety and effectiveness of these products, and that are informing their evaluation.  Adjuvants have been purchased and stockpiled in case they are needed for use under an EUA during the current emergency.  Fortunately, as noted, studies to date show that currently approved standard doses of nonadjuvanted licensed vaccines induce an excellent immune response expected to be protective against the 2009 H1N1 virus, which has remained very stable to date.

Third, we need more modern tools to assess influenza vaccines and to speed their production.  At FDA’s laboratories, and in collaboration with colleagues at CDC, NIH and globally, scientists are researching ways to improve the assays, reagents, and tests needed to more rapidly and accurately evaluate, produce, and test the quality of current and future influenza vaccines.  This work has the potential to expedite vaccine development and speed availability, and ensure vaccine quality, using the most modern scientific methods.

Fourth, ongoing scientific efforts at NIH and FDA are evaluating even more advanced approaches, such as DNA vaccines and “universal” influenza vaccines, which potentially may protect against multiple and evolving influenza strains. 

Finally, influenza is truly a global problem requiring global collaboration.  Although FDA is a WHO Collaborating Center for Influenza, and already participates in collaborative work and technical assistance through WHO and with regulatory agencies throughout the world, a much broader and deeper global collaborative effort to enhance the influenza vaccine infrastructure would be desirable and beneficial to both U.S. and global health.

Vaccines are only part of the picture.  As we respond to this pandemic, we also should take the opportunity to learn from this novel virus and the public health response, in order to promote the development of needed antivirals (which would be critical if a resistant virus should emerge), rapid diagnostics, and enhanced safety surveillance capacities, and identify remaining scientific and public health questions.  Our continued work, from basic and applied science to the medical products and public health interventions that may be used to protect people in the United States and around the world, will benefit us in preparing for and responding to biological threats, whether natural or man-made.

Conclusion

FDA is fully committed to and engaged in protecting the health of the public during this challenging time.  Among us are laboratory scientists, epidemiologists, medical reviewers, product experts, and field inspectors.  We will bring every skill and resource we have to this critical mission.  The collaboration among U.S. Government agencies has been remarkable, and interactions with the private sector and global partners have been proactive, constructive, and essential in addressing the outbreak.  I thank you for both your support for public health and for the opportunity to testify today and will be pleased to answer any questions from Members of the Subcommittees.

Last revised: June 18, 2013