Date Published: August 7, 2007
Publisher: Public Library of Science
Author(s): Michael J Brennan, Uli Fruth, Julie Milstien, Rosemary Tiernan, Sergio de Andrade Nishioka, Liliana Chocarro
Abstract: What are the regulatory challenges for testing and introducing investigative TB vaccines into countries where the disease is endemic?
Partial Text: In May 2005, the TB Vaccine Initiative of the World Health Organization (WHO) Initiative for Vaccine Research convened a working meeting of regulators, investigators, and clinicians from developing and developed countries involved in tuberculosis (TB) vaccine regulation and research (see Text S1 for a list of participants). The purpose of the meeting was to specifically discuss the regulatory challenges for testing and introducing investigative TB vaccines into countries where the disease is endemic.
As new vaccines are developed for TB and other infectious diseases that have an enormous impact on developing countries, clarification of the regulatory issues surrounding the development and possible licensure of these vaccines is becoming increasingly important.
An effective vaccine to both prevent TB and reduce its transmission is urgently needed because of the complexities surrounding the diagnosis, management, and treatment of TB, coinfection with TB and HIV, and challenges related to the treatment of drug-resistant Mycobacterium tuberculosis strains. Fortunately, several new TB vaccine candidates have been identified and a few have been formulated into vaccine products that are currently in phase I or II clinical trials [1,2]. A summary of first-generation TB vaccines currently in clinical trials and the next generation of TB candidate vaccines in various stages of development is provided in Table 1.
To date there is no clear global regulatory pathway for new TB vaccine candidates; thus there is an urgent need to develop a “regulatory plan” prior to the start of phase III trials, which are just a few years away. Many of the regulatory issues to be addressed are in highly technical areas, such as characterization of the product using GMP, where the US Food and Drug Administration (FDA) and the European Agency for the Evaluation of Medicinal Products (EMEA) have vast experience. Experienced regulatory agencies, such as the FDA and EMEA, can contribute to the process by: (1) reviewing investigational new drug submissions for vaccines undergoing clinical trials (FDA) or (2) providing a scientific opinion for vaccines manufactured in Europe for use in developing countries but not in the European market (EMEA). In addition, the FDA and EMEA may work with individual national regulatory authorities or with networks of regulators in the regions, and/or provide experts to global or regional panels advising on vaccine safety and efficacy issues as well as on clinical trial protocols.