The globalisation of regulatory requirements and the development and availability of medicinal products in developing countries: quality, efficacy and safety issues
DND Working Group Expert Paper
Introduction
During the twentieth century, we witnessed a therapeutic revolution which allowed, among other developments, control of cardscourgeiovascular disease and the hope of controlling cancer. In addition, while infectious diseases are still a threat, they are no longer the they once were, at least in developed countries1. These changes could not have taken place without the establishment of sound regulatory standards to provide an infrastructure conducive to research and development (R&D), and the marketing of an average of 55 new chemical entities (NCEs) a year. Between 1975 and 1999 the private R&D-based pharmaceutical industry world-wide marketed 1393 NCEs, whose pharmaceutical dossiers – based on criteria of quality, safety and efficacy – were approved by Western drug regulatory authorities (DRAs).
Regulating the pharmaceutical sector has been a constant effort of national governments, undertaken in order to “promote the protection of human health and of consumers of medicinal products” and trying to preserve a balance between conflicts of divergent interests: those of industry (driven by a logic of commercial productivity) and those of ill-informed and disorganized consumers3. The history of pharmaceutical legislation and regulation over the past century has been, in the main, a response to a series of public health policy and/or industrial failures, concerning first the quality issue of medicinal products (e.g., the 1906 US "Food and Drugs Act" prohibiting commerce of adulterated drugs), and then the safety issue (e.g., the 1938 "Federal Food, Drug, and Cosmetic Act" passed by the US Congress following a massive poisoning by an elixir of sulphanilamide containing the solvent diethylene glycol; following the thalidomide case in 1962, the US “Kefauver-Harris” drug amendments, and the European Council Directive 65/65/EEC requiring from drug manufacturers to prove to DRAs the safety and effectiveness of their products before marketing)4. In parallel the World Health Organisation (WHO) – as embodied in its 1946 Constitution and as a demonstration of its normative activities – encouraged the establishment of global standards and guidelines such as technical standards relating to the quality of medicinal products (e.g., good manufacturing practices or GMP, International Pharmacopoeia) and clinical trials supervision (e.g., good clinical practice or GCP, good laboratory practices or GLP)5.
Once pharmaceutical industry has expanded its operations beyond national borders, the ability of an individual state to safeguard public interests through specific national regulation has diminished. Whatever the activities of WHO, and however they are carried out, no effective and consistent set of laws and regulations has emerged at the international level to hold transnational corporations uniformly accountable in all countries where they operate. Instead, policies of global harmonisation of regulatory requirements have been put forward, particularly by industrialised countries. In the pharmaceutical sector, an important example of this is the work of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) during the 1990s, coordinated by pharmaceutical trade associations and the DRAs of the EU, Japan and the USA6. The driving force behind this has been the increase in global trade in medicinal products, the increasing complexity of country-based technical regulations related to drug safety, efficacy and quality, and above all, the need for the pharmaceutical industry to bring NCEs to market faster, in a wider market, and at a reduced cost in order to achieve an acceptable return on R&D investments. This current trend towards industry self-regulation or co-regulation with DRAs is now regarded as a more pragmatic and realistic way than promulgating binding international regulations. It has become all the more plausible as transnational corporations have gained so much power that they can hardly be regulated by externally-defined rules and laws, and because WHO appears to put its legally-binding normative activities aside, giving more importance to “constructive public-private partnerships and dialogues”7.
This briefing paper attempts to shed some light on a kind of “creeping privatization” of the framework of international regulation, beginning by reviewing the various processes of harmonization, and the general impact of the globalization of regulatory and technical standards on the development and availability of medicinal products; particularly for developing countries, which are excluded from this process. The impact of ICH in non-ICH countries is then analysed through a “case study”, comparing ICH and similar guidelines to WHO guidelines on quality issues.