Development of New Tuberculosis Vaccines: A Global Perspective on Regulatory Issues

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 specifi cally discuss the regulatory challenges for testing and introducing investigative TB vaccines into countries where the disease is endemic. A particular focus of this meeting was a discussion among representatives of regulatory authorities from the Developing Countries Vaccine Regulators Network (DCVRN) with those of the United Kingdom and the United States about the important challenges that each regulatory agency will need to address if effective new TB vaccines are to be registered in their countries. The DCVRN is a new WHO initiative establishing a network of vaccine regulators from nine countries: Brazil, China, Cuba, the Republic of South Korea, India, Indonesia, the Russian Federation, South Africa, and Thailand. It provides a forum for discussion, advancement of knowledge, and exposure to policies and procedures pertaining to evaluation of clinical trial proposals and clinical trial data. In this article we describe key vaccine and regulatory issues arising during the meeting. We propose innovative recommendations that may be used to make important decisions for proceeding into various stages of clinical trials and for the fi nal registration of new TB vaccines. We hope that this article will be particularly valuable to regulatory authorities of developing countries. TB Vaccine Development: The Regulatory Challenges As new vaccines are developed for TB and other infectious diseases that have an enormous impact on developing countries, clarifi cation of the regulatory issues surrounding the development and possible licensure of these vaccines is becoming increasingly important. In countries where national regulatory authorities (NRAs) are robust and have experience in the steps leading to marketing authorization for innovative products, there may not be an appropriate population in which to conduct clinical trials to establish the safety and effi cacy of a new TB vaccine. Regulatory authorities in developed countries may lack suffi cient experience with the disease burden of the target and other concomitant diseases. In addition, these regulatory agencies may be unfamiliar with medical treatment norms in countries with a high burden of TB. All these obstacles make it diffi cult for regulatory authorities in developed countries to address some of the regulatory and clinical development issues for TB vaccines. Conversely, in countries where TB is more prevalent, the regulatory agencies may be relatively inexperienced in the regulation of “fi rst in human” products, or may lack the resources and regulatory framework to guide the development of a new TB vaccine product. Development of New Tuberculosis Vaccines: A Global Perspective on Regulatory Issues Michael J. Brennan, Uli Fruth, Julie Milstien, Rosemary Tiernan, Sergio de Andrade Nishioka, Liliana Chocarro, and the