Renovation of the new medicine regulatory process

As we near the end of the first decade of the 21st century, it is obvious that the discovery, development, and commercialization of new medicines is a dynamic process that has become vastly more complicated than it was even a few years ago. It is an international process involving companies located in many different countries, clinical trials performed in even more countries and academic contributions from around the world. There are many hundreds of drugs in clinical development. They are representatives of multiple technologies and chemical classes including small molecules, monoclonal antibodies, other proteins, anti-sense oligonucleotides, aptamers, and gene therapy, and, perhaps in the near future, stem cell-based therapeutics. These clinical trials are sponsored by very large multinational pharmaceutical and biotechnology companies with very substantial experience, generic companies, traditional regional companies expanding toward worldwide markets, and biotechnology companies that range in size and competency from very large and experienced to virtual with virtually no experience. The trials are, in fact, often conducted by contract research organizations that again vary widely in size, competency, and experience. All of this is managed by a very uneasy collaboration between the industry, academic medicine, and regulatory agencies. Expectations for the development of new medicines have changed substantially as well. There is greater focus on demonstrating long-term safety. Efficacy trials have become much larger, more complicated and even more multinational. Further, in many therapeutic areas there is increasing demand for long-term outcome studies. These factors contribute to progressively costlier and more time-consuming development cycles that are coupled to longer regulatory review processes, more rapid emergence of competitive products and shorter effective patent lives. These factors, in turn, put more pressure on companies to extract the maximum in sales and profits as rapidly as possible after commercialization, resulting in even greater reliance on direct-to-consumer advertising and efforts to encourage as broad a use of the new medicines as possible. Contemporaneously, food and food processing, nutritionals, vitamins and supplements, cosmetics, and diagnostic industries have also become much more complex. In response, the FDA has grown. It has promulgated new rules and guidelines in virtually every area. It has imposed user fees on the industries it regulates and is buffeted by conflicting demands to facilitate the development of new products, yet reduce risk to unachievable levels. The net result is that no one is satisfied. Patients and patient advocacy groups quite correctly complain about limited progress. The industries contend that the regulatory processes are intrusive, cumbersome, and are applied capriciously. The FDA is criticized consistently and it has been difficult for the agency to recruit and retain outstanding individuals. In contrast to the dynamic changes recorded by all the regulated industries, science and medicine, the delivery of healthcare, information technologies and media coverage, the legal basis and charter of the FDA have changed little since the last major overhaul of the legislation in 1962 (1–3). Little wonder then that few, if any, are satisfied with the job that the FDA is doing today. Proposals to institute a systemic overhaul of regulatory processes have been made, but major changes have not been implemented (4). Despite the fact that there has been no total overhaul of the regulations covering the development of new medicines, there have been quite a number of new initiatives that are both laudable and establish some of the bases needed for even more significant changes. Most of these COMMENTARY