FDA is Working Closely with Manufacturers of Meningitis B Vaccines

By: Karen Midthun, M.D.

Meningitis has been in the news recently because of outbreaks of a specific strain (called “serogroup B” or “MenB”) on college campuses. Infections caused by MenB are uncommon in the U.S, but can be very serious. According to the Centers for Disease Control and Prevention (CDC), 160 of the 500 cases of meningococcal disease in the U.S. in 2012 were caused by MenB. There are vaccines licensed (approved) in the U.S. to prevent meningitis, but none include this strain.

Dr. Karen MidthunTo address this critical public health need, FDA worked closely with CDC, in order for CDC to make an unapproved MenB vaccine available as quickly as possible to the universities where CDC determined outbreaks had occurred. This was accomplished under FDA’s expanded access program for investigational (or unapproved) products. The program allows the use of unapproved drugs or vaccines to treat or prevent serious or immediately life-threatening conditions when other options are not available.

FDA has been working closely with manufacturers pursuing the development and approval of MenB vaccines for the U.S. The approval of any vaccine in the U.S. is an extensive process that requires submission of a Biologics License Application (or BLA) by a manufacturer. FDA medical and scientific staff then perform a detailed review of data supporting the safety and effectiveness of the vaccine, and FDA staff inspect the quality of the manufacturing process. Because the potential usefulness of a preventative vaccine must be weighed against any unintended side effects, the evaluation of each submission includes a careful assessment of the benefits and risks to public health.

The agency has a variety of regulatory tools – breakthrough therapy designation, accelerated approval, the fast-track program, and priority review – that have enabled FDA to help make innovative and effective new treatment options available to patients more rapidly for serious conditions such as MenB. More information about these programs is available on FDA’s web site.

Although the law generally prohibits FDA from disclosing the existence of pending applications, Novartis has given the agency permission to disclose that the firm plans to submit a BLA for Bexsero (serogroup B meningococcal vaccine) for review in the second quarter of 2014. Pfizer, which also is developing a serogroup meningococcal B vaccine, issued a statement on March 20, 2014, in which it acknowledged receiving breakthrough designation from the FDA for its vaccine, and that it intends to submit an application for review by mid-2014.

FDA is committed to working with manufacturers to bring important medical products to patients as quickly as possible. The health and well-being of patients is our top priority.

Karen Midthun, M.D., is the director of FDA’s Center for Biologics Evaluation and Research

We’re Working to Offset Ameridose Impact

By Margaret A. Hamburg, M.D.

Drug shortages are two words that no one wants to hear—not patients, not health care professionals, and not me.

Margaret Hamburg, M.D.FDA has been working hard to prevent and mitigate drug shortages. In 2011, the number of medications in short supply hit 251. Addressing drug shortages must be a top priority for us at FDA because these are medications that people need to stay healthy, to treat their illnesses, and even, in some cases, to stay alive.

This year, we’ve taken significant steps to expand our efforts and to engage in new ways with industry. Between Jan. 1 and Sept. 30, 2012, FDA worked with drug manufacturers to help avert the shortage of 145 drugs. Many critical medicines used to treat cancer and conditions such as attention deficit hyperactivity disorder (ADHD) are no longer in short supply.

However, drug shortages are still a serious problem, one that may be temporarily impacted by Ameridose LLC’s voluntary recall of all of its unexpired products. Ameridose, located in Westborough, Mass., is managed by some of the same people as the New England Compounding Center—which produced the drug that is implicated in the deadly, multi-state outbreak of fungal meningitis. An inspection of Ameridose was initiated as part of FDA’s ongoing investigation of the outbreak.

FDA recommended that Ameridose recall its sterile drugs because we could not be assured of the sterility of those products. However, this recall may affect supplies of certain life-saving drugs for some health care systems. FDA has identified a number of Ameridose products—including drugs used during surgery and to treat medical conditions that include congestive heart failure—that were on the current drug shortages list before the recall.

We also know that the supply of other drugs may be affected by the Ameridose recall. That’s why FDA is taking proactive steps to minimize the impact this recall may have on current drug shortages, and to prevent other shortages from occurring.

For recalled medications on the current drug shortages list, FDA is taking the same actions it has used successfully to mitigate other shortages.

  • FDA is working with manufacturers of these drugs, requesting that they ramp up production if they are willing and able to do so.
  • For any manufacturers of these drugs that may be experiencing manufacturing or quality problems, FDA is offering assistance to enable them to produce shortage drug products that are safe and high quality.
  •  As with shortages of any critical products, FDA will expedite the reviews of any pending applications that could help with addressing the shortages.
  • FDA is identifying any additional manufacturers willing to initiate or increase production.
  • If manufacturers of critical drugs are not able to meet U.S. patient needs, FDA will explore overseas companies that are willing and able to import foreign drugs to address the shortage. In these instances, FDA evaluates the imported drug to ensure that it is of adequate quality and that the drug does not pose undue risks for U.S. patients.

Since the beginning of the year, the number of advance notifications to FDA of potential shortages has greatly increased. If we know that a problem is on the horizon, we’re able to proactively work with industry, organizations, patients and stakeholders to address it. We have doubled the number of staff members who work in drug shortage prevention and response.

We at FDA are committed to doing everything we can, using all available tools, to prevent or mitigate drug shortages and help keep critically needed products on the market.

Margaret A. Hamburg, M.D., is Commissioner of the U.S. Food and Drug Administration.

FDA Assists in the Success against Epidemic Meningitis in Africa

By: Marc Kusinitz, PhD

Meningococcal meningitis, a disease that sweeps across sub-Saharan Africa in an area called the meningitis belt, is losing its power to inflict illness and death. Scientists from FDA made a critical contribution in developing the technology needed to manufacture a vaccine against this terrible disease, and at an affordable cost for African nations like Burkina Faso, Chad, Ethiopia, and Niger.

Meningococcal meningitis can be deadly. It kills 10 percent of people it infects within two days after they start showing symptoms. Although an antimicrobial drug saves large numbers of infected individuals, about 10 percent die from the infection and about 10 percent to 20 percent of survivors develop mental retardation, hearing loss, or seizures. In Africa, most meningococcal disease is caused by the group A meningococcus bacteria, and about half of its victims are working-age adolescents and young adults. The disease results in very significant human, social, and economic losses to the affected communities and countries. Vaccination offers the best chance to prevent the disease and epidemic meningitis. However, an existing vaccine didn’t work very well.

Developing a Vaccine:

In 2001, the Bill & Melinda Gates Foundation agreed to fund the Meningitis Vaccine Project (MVP)–a partnership between the World Health Organization and PATH, a non-profit organization based in Seattle, WA that works with collaborating groups to provide health care technologies and strategies to areas of the world that have limited resources.

Dr. F. Marc LaForce led MVP’s effort to develop, test and license a new type of vaccine against group A meningococcus bacteria, that could protect people before an epidemic begins. The new vaccine, called a conjugate, is a chain of sugars connected to a protein that the immune system responds to very well. When MVP hit a hurdle during the development stage, FDA stepped in. Drs. Robert Lee and Carl E. Frasch, two researchers in the Office of Vaccines Research and Review in FDA’s Center for Biologics Evaluation and Research (CBER), had developed an alternative conjugation technology that was more efficient and less costly. Through a technology transfer agreement, FDA provided the technology to MVP via PATH, with help from the National Institutes of Health.

Scientists at CBER also developed reagents for evaluating the vaccine’s performance and safety and developed methods to monitor the manufacturing process. MVP had partnered with the Serum Institute of India Limited, a developing-country vaccine manufacturer, to make the new conjugated vaccine. In December 2003, two scientists from the Serum Institute came to Drs. Lee and Frasch’s FDA laboratory to learn the conjugation method to manufacture the vaccine.

After preclinical animal studies and a series of clinical trials in people in India and Africa’s meningitis belt to assess its safety and effectiveness, the new vaccine, MenAfriVac, was licensed in Dec. 2009 by India for export to Africa. By June 2010, the WHO had prequalified the vaccine for use in global immunization programs.

Woman Receiving Vaccination

September 2010. A woman in Mali receives MenAfriVac in an early introduction in preparation for the official vaccine program launch in December. Photo: WHO/Mali

Launching the Vaccination Campaign:

MVP launched its vaccination campaign in Dec. 2010, beginning in Burkina Faso and moving on to Mali and Niger and eventually Cameroon, Chad and Nigeria. By the end of 2011, an estimated 55 million people had been vaccinated with MenAfriVac at a cost of only 40 cents per dose.

The contribution of CBER researchers Carl Frasch and Robert Lee was perhaps best summed up by MVP director Dr. LaForce in a news story about their timely contribution of the conjugation technology that enabled the development of MenAfriVac at a price that Africa could afford: “These guys are heroes.”

FDA’s contributions to a major health care project in Africa underscore the agency’s recognition that infectious diseases know no borders. Protecting human health globally is linked to the agency’s core mission of protecting human health in the United States.

Marc Kusinitz is Senior Science Communications Advisor in FDA’s Center for Biological Evaluation and Research