Inhalation Products Expert Groups: Helping to Fill the Gaps

Steve Nichols, PhD (Aventis, Cheshire UK) and Svetlana Lyapustine, PhD (Gardner Carton & Douglas, Washington, DC)

Since the advent of the first medicinal inhalers in the late 1950s, the area of inhalation medicine has expanded rapidly. Today, the scope of devices producing pharmaceutical aerosols encompasses propellant-driven pressurized metered dose inhalers (MDIs); dry powder inhalers (DPIs) containing premetered capsules of powdered drug or sophisticated systems for measuring and dispersing fine powder; hand-held electromechanical devices delivering a fine, inhalable aqueous-based spray; and many other creative mechanisms. This diversity of delivery systems is in part a result of the international ban on CFCs (see http://www.fda.gov/cder/mdi/default.htm) and in part a result of the growing variety of molecules targeted for pulmonary delivery. In recent years, the number of active molecules delivered by means of the pulmonary route and the number of therapeutic indications also have increased dramatically. Respiratory diseases are an obvious target, but now delivery systems for many systemic indications are in development, with inhalable insulin products for diabetes seeking regulatory approval. Much scientific work is conducted during drug development to ensure that pharmacological, mechanical, and chemical aspects of the final product (drug and inhaler) work together to produce a suitable product for its intended use. Before these drug products can reach the patient, however, the sponsor pharmaceutical company and pertinent government regulatory agencies must establish, along with proof of human safety and efficacy, certain tests and criteria to ensure that the quality of the product manufactured commercially will be the same as the product evaluated in the clinical trials. The task of developing relevant and scientifically meaningful tests and specifications is based in part on information contained in industry’s product submissions and applications to regulatory agencies. On the basis of their experience, regulatory agencies summarize regulatory requirements in guidance documents for industry. These guidances serve an important role by preserving institutional knowledge, enhancing consistency and predictability of regulatory reviews, and setting common targets for pharmaceutical product development. Nonetheless, the process of developing and publishing formal regulatory documents by government agencies may not keep up with the need of the industry for clear, comprehensive, and contemporary guidance on technical issues. On the other hand, regulatory guidances that are issued sometimes highlight areas where the regulatory approaches could be improved. Expert groups help to fill these gaps in the development of regulatory guidance. First, expert groups can develop and present scientifically supported arguments to provide needed guidance or affect a change in existing guidance. Furthermore, expert groups can assess and publish industry best practices on selected topics. Expert groups also help increase awareness of the scientific, industrial, and regulatory community and help to remove barriers. Finally, in achieving these goals, expert groups advance the science of inhaled drugs. Expert groups are not tied to any particular company or product, and they usually operate on a consensus agreement approach. At their best, they foster open scientific discussion of common technical problems, generate data, review and interpret available information, and offer their expert advice to both industry and regulatory agencies. Over the years, various types of expert groups have emerged (see Figure 1), both in Europe and in the United States, that are either directly or indirectly associated with inhalation delivery standards. This article provides an overview of today’s expert group landscape. It is a tribute to the work of all experts who look for constructive solutions to difficult technical problems, build communication within industry and between industry and regulators, fill gaps in our understanding, and stimulate the overall advancement of science, technology and regulation—all of which facilitates and expedites the provision of innovative and improved drug products to patients. (continued)