Research Article: The US Food and Drug Administration Provides a Pathway for Licensing Vaccines for Global Diseases

Date Published: July 21, 2009

Publisher: Public Library of Science

Author(s): Michael J. Brennan

Abstract: None

Partial Text: Responding to an urgency for new vaccines for global diseases, in September 2008 the Center for Biologics Evaluation and Research (CBER) at the US Food and Drug Administration (FDA) published an important FDA Guidance Document (see Box 1), “General Principles for the Development of Vaccines to Protect Against Global Infectious Diseases,” [1] that should expand the FDA’s role in facilitating the development of new vaccines for global bacterial, viral, and parasitic diseases affecting millions of people in developing countries worldwide. In part, this action is in response to a changing paradigm in advocacy for global diseases and recognition on the part of developed nations that the facilitation of vaccines and other products for neglected diseases disproportionately affecting those living in poverty is an effort that benefits industrialized as well as low-income countries. Moreover, through the effort of researchers, the pharmaceutical and biotechnology industries, and guided by nongovernmental product development partnerships, many funded by the Bill & Melinda Gates Foundation, preventative vaccines for global diseases are becoming a reality. Recent progress in this area is exemplified by both a meningococcal vaccine [2] and a new malaria vaccine moving forward into phase III efficacy trials in several African nations [3] and by several candidate vaccines for the prevention of tuberculosis being tested in phase I and II trials [4]. Vaccines and therapeutics for other viral [5], bacterial [6], and parasitic [7] neglected diseases are also in various stages of progress.

To address the gap in regulatory pathways for global vaccines, the FDA’s new guidance document provides an additional solution by indicating that (1) the FDA can license vaccines to protect against infectious diseases or conditions not endemic in the US, (2) the regulatory pathway is the same as for vaccines licensed for use in the US, and (3) the clinical data from trials conducted outside the US can be used for licensure. The principles in this document are supported by legislation, including the Food and Drug Administration Amendments Act of 2007 section 524, which recognizes the importance of accelerating the development of products that prevent diseases for which there is no market in the US. The document is an important declaration, for it ensures that a vaccine for a disease not endemic to the US can be considered for licensure if it has been shown to be safe and effective under the FDA’s Investigational New Drug process. The Investigational New Drug process is particularly thorough in that it provides the vaccine sponsor with a complete review of (1) the purity of the product and (2) the nonclinical data, which ensures that the product is manufactured correctly each time. It also uses an independent analysis of the clinical trial results, which, along with the review by an FDA Advisory Board of experts, provides reliable advice on the safety and effectiveness of the new vaccine. Licensure by the FDA provides a strong foundation for countries that lack well-resourced regulatory agencies to consider this new vaccine for registration in their countries. As mentioned, it also facilitates WHO’s ability to approve this new vaccine for global distribution through its vaccine prequalification and procurement process. The new FDA guidance also points out that vaccines for global diseases may meet the requirements for “accelerated approval,” which can significantly shorten the timelines for licensure in the US, or for designation as an “orphan drug,” which provides for a waiver of FDA user fees usually required for vaccine licensure.

It is clear, however, that the success of this promising FDA initiative will depend both upon the vaccine developers’ willingness to submit their products to the rigorous FDA review process and on the FDA’s ability to effectively implement the new recommendations. There are likely to be significant challenges for FDA reviewers. Although even a partially effective vaccine can have a major impact on diseases like tuberculosis, the FDA has traditionally not licensed vaccines with efficacy below 80%. The guidance document does not describe the principles FDA will use to license a vaccine that has efficacy levels unlikely to be accepted in the US but determined to be at a level that would save hundreds of thousands of lives annually in a country or a region where the disease is epidemic. Other questions are raised by the document. For example, how would a malaria vaccine for children be labeled for use if there is no US target population? Will developing countries be concerned that CBER/FDA could potentially use a different standard for review of products that will only rarely be used in the US? Will the cash-strapped FDA be given the resources to implement this new mandate? And finally, since this document addresses vaccines specifically, are similar licensing guidelines followed for drugs, therapeutics, and diagnostics?



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